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A Ciavattini

Publications and source records attributed to A Ciavattini.

At least 37 records · Page 2Linked to original sources
PubMed1996

The 72-kDa metalloproteinase immunostaining in cervical carcinoma: relationship with lymph nodal involvement.

OBJECTIVE: In the present study we detected 72-kDa metalloproteinase expression in our series of early stage cervical carcinomas and analyzed the relationship between 72-kDa metalloproteinase staining and risk of nodal involvement with the goal of identifying a parameter useful in predicting the metastatic potential of lesions. MATERIALS AND METHODS: The medical records of 34 patients with FIGO stage I squamous cell cervical carcinoma who had undergone primary radical surgery with systematic pelvic and para-aortic lymphadenectomy (Piver's type III) at the Institute of Gynecologic and Obstetrics, Ancona University, between January 1988 and January 1993 were recruited from our series of 57 consecutive cases and reviewed. Any characteristic that could be relevant for prognosis was recorded in all of the cases: histologic grade of differentiation, tumor size, lymphatic spread, and adjuvant radiotherapy. Immunohistochemical staining was performed on serial sections of tumors using the avidin-biotin complex technique (Vector Laboratories, Burlingame, CA). The affinity-purified rabbit anti-72-kDa metalloproteinase antibody was used. Positive staining was expressed as a percentage of positive cells per 10(3) counted neoplastic cells (the 72-kDa metalloproteinase index). RESULTS: The tissue 72-kDa metalloproteinase immunoreactivity was diffusely expressed in all cervical carcinomas (ranging from 8.6 to 51.9%, with a median of 17.8%) and showed a significant relationship with respect to lymphatic spread. In the presence of lymph nodal involvement, the 72-kDa metalloproteinase index was significantly higher than in the absence of nodal metastasis (32.9 +/- 12.2% versus 18.1 +/- 9.0%, means +/- standard deviations with P = 0.001); a significant relationship was also observed between the 72-kDa metalloproteinase index and the number of positive nodes (r = 0.8, with P = 0.01). No significant relationship was defined with respect to the other prognostic parameters. The Cox proportional hazard analysis showed a significant relationship between the 72-kDa metalloproteinase index and disease-free survival (P < 0.0001) that was independent of tumor size, nodal involvement, and lymphvascular space invasion. CONCLUSIONS: Although the small numbers do not allow any definitive conclusion, a significant relationship between the 72-kDa metalloproteinase index and the risk of lymphatic spread is defined in early stage cervical carcinoma. The 72-kDa metalloproteinase immunostaining seems to have a prognostic value, suggesting the possibility of an association between neoplastic aggressiveness and 72-kDa metalloproteinase expression.

Adult↗
PubMed1996

Proliferating cell nuclear antigen in endometrial carcinoma: pretreatment identification of high-risk patients.

OBJECTIVE: The aim of our study was to retrospectively examine the proliferating cell nuclear antigen (PCNA) immunoreactivity of tumor cells in curettage specimens containing endometrioid adenocarcinoma and obtained immediately before definitive surgical staging. This PCNA index was compared with the one subsequently derived from surgical specimens and assessed as a function of histologic grade, depth of myometrial invasion, neoplastic nodal involvement, cervical spread, and progression-free survival in order to determine a new prognostic parameter valuable at the time of diagnosis. MATERIALS AND METHODS: A population of 79 patients with locally advanced (stage I and II) endometrioid carcinoma, who underwent both the preliminary diagnostic curettage and the subsequent definitive surgical management, selected from January 1986 to June 1993 at the Department of Gynecology and Obstetrics, Ancona University, was retrospectively recruited from our series of 99 endometrial carcinomas. The archival paraffin blocks from the curettage and uterine specimens were identified and assessed for histologic reexamination and PCNA immunostaining [PC10 monoclonal antibody (Dako, Denmark)]. RESULTS: After a median follow-up of 47 months, recurrences were detected in 7 cases, and the Kaplan-Meier disease-free survival curve estimated for the entire study group was 91%. The median PCNA index of the curettage specimens presented a good overlap with the PCNA immunostaining in corresponding uterine samples with a correlation coefficient of 0.4 (P=0.02). A PCNA index >/=30% in curettage specimen was predictive of deep myometrial invasion; of 35 patients with PCNA index > or = 30%, 29 (83%) had myometrial invasion > or = 50%. No significant relationship was observed with neoplastic cervical spread, and histologic differentiation. By Cox hazard analysis, the PCNA index evaluated on curettage specimens was significantly related to disease-free survival, with significant disease-free survival advantages for patients with PCNA <30% (P<0.001). CONCLUSION: Our findings suggest that the PCNA immunostaining has proved to be considerably promising for the risk assessment in locally advanced endometrial carcinoma. The PCNA index is an objective and reproducible parameter accruably valuable also before starting the treatment; in presence of a high PCNA index, the patients should be referred to gynecologic oncologists for appropriate management.

Adenocarcinoma↗
PubMed1996

Recurrence patterns in locally advanced cervical carcinoma: role of nodal status and 72-kDa metalloproteinase index.

OBJECTIVE: The aim of the study was to analyze the relationship between lymph nodal involvement and regional and/or distant recurrences in locally advanced squamous cervical carcinomas, and also evaluate tumor 72-kDa metalloproteinase, as a biologic parameter useful for understanding the mechanisms of disease relapse and prognosis. In particular, 72-kDa metalloproteinase is an enzyme that specifically cleaves type IV collagen and seems to play a critical role in tumor invasion and metastatic dissemination. METHODS: The medical records of 62 patients with FIGO (International Federation of Gynecology and Obstetrics) stage Ib and IIa squamous cervical carcinoma who underwent primary radical surgery with systematic pelvic and paraaortic lymphadenectomy and then were routinely followed were recruited from our series of 76 consecutive cases and reviewed. Fifty-four patients with complete clinicopathologic information were considered eligible for the study. All recurrences were defined as histologically and/or cytologically documented disease, following a minimum 3-month disease-free interval. Sites of recurrences were classified as distant, or regional to the pelvis. Immunostaining with 72-kDa metalloproteinase was performed on serial sections of tumors using avidin-biotin complex technique. Affinity-purified rabbit anti-72-kDa metalloproteinase antibody was used. Positive staining was expressed as a percentage of positive cells per 10(3) counted neoplastic cells (72-kDa metalloproteinase index). RESULTS: After a median follow-up of 38 months (range 9-71 months), 11 patients recurred with a 20% overall incidence. Seven patients (64%) recurred regionally, with side-wall infiltration in 2 cases, and 4 patients (36%) recurred distantly. By Cox hazard multivariate analysis, lymph nodal status was significantly related to disease-free survival (P = 0.01); in particular, all the patients with side-wall or distant recurrences had lymph nodal involvement. A significant relationship was also observed between tumor 72-kDA metalloproteinase immunostaining and disease-free survival (P = 0.02). The 72-kDA metalloproteinase index was significantly higher in patients who recurred than in patients with disease-free follow-up (P < 0.001); in particular, the highest values were detected in patients who recurred distantly. A relationship between 72-kDa metalloproteinase staining and nodal status was observed (P < 0.001). CONCLUSIONS: In conclusion, nodal status and the 72-kDa metalloproteinase index were two independent prognostic parameters, significantly related to recurrence risk and pattern of recurrence in locally advanced cervical carcinoma. Although they are independent prognostic parameters, a relationship between nodal involvement and 72-kDa metalloproteinase was observed. A model of tumor recurrence in which intrinsic tumor factors exert their negative influence directly or by contributing to the development of nodal metastases seems possible.

Animals↗
PubMed1996

Microinvasive cervical carcinoma and cervical intraepithelial neoplasia: biologic significance and clinical implications of 72-kDa metalloproteinase immunostaining.

OBJECTIVE: The immunohistochemical expression of 72-kDa metalloproteinase was evaluated in cervical intraepithelial neoplasia (CIN) and microinvasive carcinoma, with the aim to define a relationship between 72-kDa metalloproteinase expression and neoplastic invasiveness, useful to identify subsets of intraepithelial lesions with higher risk of progression. MATERIALS AND METHODS: Cervical bioptic samples were obtained consecutively from 54 women who attended our Colposcopic Service from January 1993 to July 1993 because of abnormal pap smear, suspicious for cervical dysplasia and/or human papillomavirus infection. After written consent, 29 women with CIN were included in the study. All women with CIN 3 lesion underwent conization; in 21 women with mild or moderate cervical dysplasia, we did not perform any medical or physical treatment but followed them longitudinally at close interval. After 12 months, the clinical evolution was classified as spontaneous remission, persistence, or progression depending on the absence or presence of lesion and/or HPV infection in colposcopy, histology, and polymerase chain reaction findings. In the study we also included surgical specimens from 10 women with microinvasive squamous carcinoma who underwent primary radical surgery. Seventy-two kilodalton metalloproteinase positivity was immunohistochemically stained on serial sections by using the avidin-biotin complex technique (Vector Laboratories, Burlingame, CA) and expressed as percentage of cells per 10(3) counted neoplastic cells. RESULTS: Cytoplasmatic positive 72-kDa metalloproteinase immunostaining was significantly higher in microinvasive cervical carcinomas than in CIN lesion (Student's t test; P < 0.001). Considering only cervical intraepithelial neoplasias, a significant increase in 72-kDa metalloproteinase immunostaining was observed with CIN degree increasing (one-way analysis of variance; P = 0.002). No correlation was found between 72-kDa metalloproteinase immunostaining and HPV infection and lesion size defined by quadrants of the cervix involved with colposcopically evident dysplasia. By analyzing 72-kDa metalloproteinase positivity, regressive dysplasia showed low values of 72-kDa metalloproteinase immunostaining (median 1.2%, range 0.5-1.8%), while persistent (median 2.6%, range 1.9-3.6%) and progressive lesions (median 4.6%, range 2.3-6.9%) presented a significantly higher positivity (one-way analysis of variance; P < 0.001). DISCUSSION: In conclusion, the 72-kDa metalloproteinase expression is related to invasive potential with a significant increase in staining positivity in microinvasive carcinomas; 72-kDa metalloproteinase is detectable in cervical dysplasia, and it is related to the severity of cellular atypia. A clinical implication of 72-kDa metalloproteinase immunostaining seems to be indicated, by analyzing the differences in 72-kDa metalloproteinase positivity rates between regressive and persistent or progressive disease.

Adult↗
PubMed1996

Natural cytotoxicity and GnRH agonist administration in advanced endometriosis: positive modulation on natural killer activity.

OBJECTIVE: To investigate the effects of pharmacologic suppression of ovarian function on the immune system, with respect to the clinical outcome of endometriosis and the possibility of an immunoendocrine combined treatment. METHODS: After informed consent, 25 of 37 patients with revised American Fertility Society stage III and IV endometriosis who underwent postoperative medical treatment were selected and enrolled for this immunoendocrine longitudinal study. Medical treatment consisted of tryptorelinum depot injection, 3.75 mg/month for 24 weeks. Blood samples were collected before the first injection in the early follicular phase, day 2-3 of the cycle, and during medical treatment (every 4 weeks) and follow-up (every 6 months). At the end of the study, we had ten blood samples per patient to evaluate the cytotoxic activity, the number of natural killer cells, and the serum levels of estradiol. Natural killer activity was determined against the K562 cell line by target cell retention of the fluorescent dye carboxyfluorescein diacetate. RESULTS: A positive immunomodulating effect was observed during GnRH agonist administration. In particular, a significant progressive increase in natural killer cell activity was defined within the first 12 weeks of medical treatment; after three injections, we observed the highest values of cytotoxicity, with a median of 7.1 lytic units (range 0.3-14.0; P = .02). Natural cytotoxicity then decreased toward a plateau, which persisted during therapy completation and follow-up, with slight fluctuations. In patients who had recurrence, the values of natural killer cell activity were constantly lower than those in patients with disease-free follow-up, particularly within the first 12 weeks of medical treatment.

Adult↗
PubMed1996

72-kilodalton type IV collagenase, type IV collagen, and Ki 67 antigen in serous tumors or the ovary: a clinicopathologic, immunohistochemical, and Serological study.

The immunohistochemical expression of 72-kDa type IV collagenase [matrix-metalloproteinase (MMP)-21], basement membrane component type IV collagen and proliferation-related antigen Ki 67 were investigated in 43 benign, borderline, and malignant serous tumors of the ovary. The results were compared with the histotypes of ovarian serous tumors and with their clinical behavior. Serum evaluation of MMP-2 was performed in 14 patients with cystadenocarcinoma and the data compared with that of a control group. The basement membrane (BM) was continuous in benign cystadenomas and in some borderline tumors, whereas it was discontinuous or absent in other borderline tumors, in borderline tumors with microinvasion, and cystadenocarcinomas. The percentage of MMP-2- and Ki 67-expressing cells increased from cystadenomas to borderline tumors, being the highest in malignant tumors; a frequent basal disposition of the MMP-2 cytoplasmic granules also was observed in cystadenocarcinomas. Statistical analysis demonstrated that MMP-2 expression was inversely related to BM integrity. Serum MMP-2 values did not differ from that of the control group. Cox regression analysis showed that tumor stage and grade were significant prognostic factors, whereas MMP-2 and Ki 67 immunohistochemical expression added no further significant information to the prognosis. The investigators conclude that the correlation between increasing MMP-2 expression and BM alteration gives support to the hypothesis of a direct role of the metalloproteinase in the process of destructive stromal invasion. MMP-2, type IV collagen, and Ki 67 immunodetection varied according to the histologic classification of ovarian serous tumors. However, neither these factors nor the serum evaluation of MMP-2 appear useful as prognostic predictors in this series.

Antibodies, Monoclonal↗
PubMed1996

MIB 1 immunostaining in cervical intraepithelial neoplasia: prognostic significance in mild and moderate lesions.

OBJECTIVE: MIB 1 is a new monoclonal antibody which recognizes nuclei of proliferating cells throughout the cell cycle except during the G0 and early G1 phases. In the present study we analyzed the MIB 1 immunostaining as an index of cellular proliferation in cervical intraepithelial neoplasia (CIN) and microinvasive carcinoma, with the aim to identify a relationship with the degree of dysplastic lesion and the risk of neoplastic progression. A correlation between the MIB 1 index and human papillomavirus (HPV) DNA presence was also investigated METHODS: Cervical bioptic samples were consecutively obtained from 86 women who attended our Colposcopic Service from January 1993 to June 1994, because of abnormal pap smears suspicious for cervical dysplasia and/or HPV infection. On histologic evaluation, 41 women had CIN, 23 cervical condyloma, and 22 squamous metaplasia. Ten patients with microinvasive squamous cervical carcinoma, matched for age and demographic characteristics, were selected from our series of cervical carcinomas and immunohistochemically analyzed. The expression of primary tumor cellular proliferation was immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave oven-processed formalin-fixed paraffin-embedded tissue. Positive staining was expressed as the percentage of positive cells per 10(3) counted dysplastic cells for each case. RESULTS: A progressive significant increase in positive MIB 1 immunostaining was observed from squamous metaplasia to microinvasive carcinoma throughout the CIN lesions (p < 0.001). Considering only CINs, the MIB 1 index showed a significant increase with respect to CIN degrees (p < 0.001); no correlation was found between MIB 1 immunostaining and HPV infection, and lesion size. By analyzing the MIB 1 index with respect to CIN outcome in mild and moderate dysplasias, regressive lesions had lower values of MIB 1 immunostaining, while persistent and progressive lesions presented significantly higher positivity (p < 0.001). CONCLUSIONS: Our data demonstrated: (1) that positive MIB 1 immunostaining increased progressively from squamous metaplasia to CIN and microinvasive carcinoma, suggesting that neoplastic transformation is associated with a dysfunctional proliferation of cervical epithelium; (2) that there was a significant correlation between the MIB 1 index and CIN degree but not with respect to HPV DNA presence, and (3) that MIB 1 immunostaining might be useful for a clinical evaluation of mild and moderate dysplastic lesions. However, a much larger study needs to be done over a longer period of time to truly determine the value of the technique in prognostically predicting which lesions might or might not regress.

Adult↗
PubMed1995

Ki67 antigen immunostaining (MIB 1 monoclonal antibody) in serous ovarian tumors: index of proliferative activity with prognostic significance.

The purpose of this study was to evaluate the biological significance of Ki67 antigen expression in serous ovarian tumors, through the analysis of MIB 1 monoclonal antibody reactivity in cystoadenomas, borderline tumors, and invasive cystoadenocarcinomas; the correlation between this index of cell proliferation and clinicopathologic parameters (FIGO stage and grade, and disease-free survival) was also investigated in invasive cystoadenocarcinomas. Fifty-four patients with serous ovarian tumors, treated at the Institute of Gynecologic and Obstetrics, Ancona University, Italy, were used as study population; 10 women had serous cystoadenoma, 16 women had serous borderline tumor, and 28 women had invasive cystoadenocarcinoma. The expression of primary tumor proliferation related to Ki67 antigen was immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave oven-processed formalin-fixed paraffin-embedded tissue. Compared to cystoadenomas and borderline tumors, the tissular Ki67 antigen immunostaining was significantly higher in cystoadenocarcinomas, with the highest values in architectural grade 2 and 3 neoplasms (P < 0.001). Within the cystoadenocarcinomas, a relationship was observed between the measured proliferation index and disease FIGO stage, but it was not significant (P = 0.92). However, patients who recurred and/or had disease progression presented a primitive neoplasm with significantly higher expression of Ki67 antigen than that of patients with disease-free survival (P = 0.01). A significant relationship was observed between the Ki67 index and disease-free survival, independent of histologic grade and stage, evaluated by Cox hazards analysis (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

MIB 1 immunostaining in stage I squamous cervical carcinoma: relationship with natural killer cell activity.

The aim of the study was to investigate the prognostic significance of estimating tumor cell proliferation in stage I cervical squamous carcinoma by analyzing MIB 1 immunostaining with respect to the lesion size, lymphatic spread, and clinical outcome. A possible relationship between MIB 1 index and natural killer activity was also discussed. The medical records of 34 patients with stage I squamous cervical carcinoma who had undergone primary radical surgery at the Institute of Gynecologic and Obstetrics, Ancona University, between 1988 and 1993, were recruited from our series of 57 consecutive cases and reviewed. Thirty-one patients were considered eligible for the study and evaluated for age, demographic characteristics, tumor histologic grade, tumor size, lymphatic spread, and adjuvant radiotherapy. The expression of primary tumor proliferation related to Ki67 antigen was immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave oven-processed formalin-fixed paraffin-embedded tissue. The basal natural killer cell activity of peripheral blood lymphocytes was evaluated against K562 cell line and expressed in lytic units for each patient. The MIB 1 immunostaining was significantly related with tumor size (P = 0.001) and lymphatic spread (P = 0.009); in contrast, there was no relationship between grade of histologic differentiation and MIB 1 immunostaining. The Cox proportional hazards analysis showed a significant independent relationship between MIB 1 immunostaining and disease-free survival (P = 0.004). The analysis of natural cytotoxicity defined a significant inverse relationship between peripheral blood lymphocyte's natural killer activity and tumor MIB 1 immunostaining (r = -0.07, with P = 0.03). Our data defined the prognostic significance of tumor cell proliferation immunostaining, an interesting parameter correlated with the disease-free survival in locally advanced cervical carcinoma. The relationship between MIB 1 index and natural killer activity is interesting; natural cytotoxicity seems to be altered in the host with respect to the cervical carcinoma characteristics.

Adult↗
PubMed1995

Relationship between 17-beta-estradiol and prolactin in the regulation of natural killer cell activity during progression of endometriosis.

Endometriosis is an estrogen-dependent disease affecting women during their reproductive years. An abnormal immune function and, in particular, a decreased natural killer (NK) cell activity have been found in endometriosis, suggesting a role of the immune system in the pathophysiology of the disease. We have recently evidenced a significant inverse relationship between 17-beta-estradiol plasma levels and NK cytotoxicity in endometriosis patients. In this study we have investigated the combined role of 17-beta-estradiol (E2) and prolactin (PRL) in the regulation of NK cell activity during the progression of endometriosis, by evaluating the correlation among E2, PRL, and other immunomodulating neurohormones on both the cytotoxic activity and the number of NK cells in women at different stages of endometriosis. The early stages (I/II) of endometriosis are characterized by increased plasma levels of either E2 or PRL without significant alterations of NK cell activity in comparison with healthy subjects. The progression to advanced stages (III/IV) of the disease is associated with a further increase of E2 levels, a decrease of PRL plasma concentrations (with an increase of E2/PRL ratio), and an impairment of NK cytotoxicity. The plasma levels of both E2 and PRL and the E2/PRL ratio are significantly correlated with the values of NK cytotoxicity in advanced stages of endometriosis. Either the absolute number or the relative percentage of CD16+ or CD56+ peripheral lymphocytes are not significantly different between patients at either stages I/II or III/IV and healthy controls. Plasma levels of progesterone (P) and luteinizing hormone (LH), are not significantly changed in different stages of endometriosis with respect to healthy controls. The significant decrease of follicle-stimulating hormone (FSH) plasma levels found in either stages I/II or III/IV endometriosis patients is not correlated with the NK cell activity. In conclusion, at advanced stages of endometriosis the impairment of NK cell activity occurs with increased E2, and decreased PRL plasma levels. Additional studies are required to determine whether the E2/PRL ratio represents a possible biochemical marker of endometriosis.

Adult↗
PubMed1995

Modulation of expression of p53 and cell proliferation in locally advanced cervical carcinoma after neoadjuvant combination chemotherapy.

OBJECTIVE: In the present study, we investigated changes of p53 expression and the cell proliferation index detected with MIB 1 in tumors before and after neoadjuvant combination chemotherapy with respect to the outcome of the disease. Our aim was to define more appropriately the significance of chemotherapy in locally advanced cervical carcinoma. MATERIALS AND METHODS: Our study included 17 women with locally advanced squamous cervical carcinoma who had been admitted to the Institute of Gynecology and Obstetrics Ancona University, between January 1990 and December 1994. The patients received neoadjuvant combination chemotherapy consisting of three cycles of cisplatin (80 mg/m2) and bleomycin (30 mg/m2). After chemotherapy, radical surgery was performed. Bioptic specimens were obtained from cervical tumors before and after chemotherapy and processed for immunohistochemical staining with a monoclonal antibody against p53 and with the monoclonal antibody MIB 1. RESULTS: Thirteen patients (76.5%) showed a clinical response (4 complete and 9 partial), while of the remaining 4 cases (23.5%) 3 had no change and 1 showed progression after neoadjuvant combination chemotherapy. A significant relationship was observed between the overexpression of p53 and the sensitivity to chemotherapy; responder patients showed a higher frequency of p53 positive cells than non-responders (P = 0.03). No significant relationship with MIB 1 index was observed. Both expression of p53 protein (P < 0.001) and reaction with MIB 1 (P = 0.003) significantly decreased after chemotherapy. The decrease in expression of p53 protein and staining with antibody MIB 1 was particularly evident in patients who responded to chemotherapy. DISCUSSION: In tumors, p53 protein and index of proliferating cells as determined with MIB 1 showed a significant modulation after treatment, suggesting an association with sensitivity to chemotherapy. However, the limited number of our series of patients does not permit a statement on the clinical implication of expression of p53 and cell proliferation in patients undergoing neoadjuvant combination chemotherapy for locally advanced cervical carcinoma.

Adult↗
PubMed1995

Cervical dysplasia in HIV-seropositive women: role of human papillomavirus infection and immune status.

OBJECTIVE: In the present study we investigated the cytologic and colposcopic characteristics of a cohort of HIV-infected women, with the aim to determine a relationship between immunologic status and frequency and/or severity of cervical abnormalities. MATERIALS AND METHODS: 21 women, who tested positive for the HIV antibody and who were admitted as outpatients because of various gynecologic complications or because of an HIV infection that was under regular clinical surveillance. A pelvic examination was performed and Papanicolaou smears were obtained from endocervix and ectocervix before colposcopic examination. Cytologic samples for human papillomavirus (HPV) detection by polymerase chain reaction were also collected. Results obtained in the group of HIV-infected women were compared with findings in a group of 473 seronegative women recruited consecutively from our outpatient population. Serum samples for T lymphocytes were drawn within 2 weeks of cytologic and colposcopic examination. CD4 and CD8 monoclonal antibodies were purchased from Becton Dickinson (Mountain View, Calif., USA). RESULTS: HIV-infected women had a significantly higher percentage of HPV DNA positivity with respect to the outpatient population (67 vs. 7%, respectively, p < 0.001). Analysis of cytologic specimens revealed 9 women (43%) with cytologic evidence of cervical dysplasia in the HIV-seropositive group vs. 23 (5%) of 473 in the outpatient population (p < 0.001). All the HIV-seropositive women with cervical dysplasia presented an associated HPV DNA positivity; in particular, the percentage of associated HPV DNA type 16 in cervical dysplasia was 78% (7/9 cases). In HIV-infected women, the evaluation of T lymphocyte subset distribution suggested a significant relationship between CD4+ cell decrease and severity of cytologic findings (p = 0.03). DISCUSSION: The HIV-infected women had a tenfold higher prevalence of both HPV infection and cervical dysplasia than the outpatient population; this increased risk seems to be limited mainly to those who also had genital HPV infection. The analysis of immunologic status confirmed previous observations that an impaired immune system results in increased cervical disease.

Adult↗
PubMed1995

Natural killer cell activity in patients with invasive cervical carcinoma: importance of a longitudinal evaluation in follow-up.

OBJECTIVE: To analyze longitudinally the basal natural killer cell activity in patients with invasive cervical carcinoma, the natural cytotoxicity was related to the most important known prognostic factors, and evaluated with respect to the clinical outcome of cervical disease. MATERIALS AND METHODS: Forty-six patients with histologically proven invasive cervical carcinoma treated and followed at the Institute of Gynecology and Obstetrics, Ancona University, Salesi Hospital, were consecutively recruited from 1989 to 1992 and included into the study. For immunologic investigation, natural killer cell activity and peripheral blood T-lymphocyte subsets were tested before primary treatment and during the follow-up period, every 6 months. Natural killer activity was determined by target cell retention of the fluorescent dye carboxyfluorescein diacetate; the K 562 cell line was used as target cells. RESULTS: A significant inverse relationship was observed between natural killer activity and disease stage (p = 0.001); patients with stage IV disease had the lowest level of natural cytotoxicity. The reduction of natural cytotoxicity was not accompanied by any alteration of lymphocyte distribution. The longitudinal analysis showed an increase of natural killer activity after surgical removal of the tumor, persisting during the follow-up, but all the 9 patients who recurred showed, at the time of disease recurrence, a significant decrease of their natural cytotoxic potential. CONCLUSION: Natural killer cell activity seems to be a functional index of immune status, significantly related to the stage and the clinical outcome of disease.

Adenocarcinoma↗
PubMed1995

HPV DNA positivity and natural killer cell activity in the clinical outcome of mild cervical dysplasia: integration between virus and immune system.

The objective was to examine the prevalence of human papillomavirus (HPV) DNA infection in mild cervical dysplasia and to evaluate longitudinally the persistence of HPV DNA positivity in an observational study, aiming at identifying the role of peripheral blood lymphocyte natural killer activity in the natural history of dysplastic disease. Twenty-three patients with histologically proven mild cervical dysplasia were selected. The HPV DNA positivity, determined by polymerase chain reaction, and cervical dysplasia were monitored cytologically and colposcopically at the 3rd (time 1), 6th (time 2) and 12th months (time 3), and defined by biopsies for routine histology taken at times 2 and 3. For each patient included in the study, the immune reactivity was evaluated at the time of diagnosis and afterwards, longitudinally during the follow-up. The immune status analysis included T lymphocyte subsets (CD3, CD4, CD8, CD56, CD16 monoclonal antibodies by Beckton Dickinson, Mountain View, Calif., USA) and determinations of natural killer cell activity (against the sensitive cell line K 562). Eighteen out of the 23 women with mild cervical dysplasia (78.3%) were found positive for HPV DNA, with a significantly high representation of HPV DNA type 16 (55.6% of cases). At the end of the study, 12 out of 18 HPV-DNA-positive women became negative (defined by two or more negative tests) for the original HPV DNA type, with 66.7% of spontaneous HPV DNA negativization rate (p = 0.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Nodal immune reactivity in FIGO (International Federation of Gyn-Ob) Stage I endometrial carcinoma: relationship with myometrial invasion.

BACKGROUND: To evaluate T lymphocyte subsets in pelvic and paraortic lymph nodes, in patients with FIGO stage I endometrial carcinoma at different degrees of myometrial invasion and with lymphovascular space invasion. The aim was to define an eventual modulation of regional immune reactivity useful in the therapeutic approach of the disease. METHODS: Twenty-two women with FIGO stage I endometroid adenocarcinoma were consecutively recruited and selected for immunological study. All the patients underwent primary surgery characterized by radical hysterectomy (Piver's type III) with bilateral salpingo-oophorectomy and systematic pelvic plus paraaortic lymphadenectomy. Lymphocyte tipization was performed by Beckton Dickinson monoclonal antibodies (CD4, CD8, CD56 and CD16) immunohistochemically in frozen-sections (immune assay on lymph nodes). For statistical evaluations. Student's t test and one way analysis of variance were used. RESULTS: Significantly higher percentages of CD4+ lymphocytes were found in pelvic than in paraaortic lymph nodes; however, by analyzing T lymphocyte content in the different pelvic nodal groups, we also observed significantly higher percentages of CD16+ and CD56+ cells in obturator nodes when compared to iliac stations. A significant increase of CD16+ and CD56+ cell percentages was then defined with respect to myometrial involvement and lymphovascular space invasion, in pelvic nodes. CONCLUSIONS: From our results, we could not define any clinical importance of nodal lymphocyte distribution in patients with early stage endometrial carcinoma; however, the observed nodal immune reactivity in presence of myometrial invasion seems interesting, with or without lymph vascular space involvement as possible expression of neoplastic systemic diffusion.

Adenocarcinoma↗
PubMed1995

Natural killer activity in stage III and IV endometriosis: impaired cytotoxicity and retained lymphokine responsiveness of natural killer cells.

Our objective was to investigate the role of estrogens in the development and progression of endometriosis, and evaluate the in vitro boosting effect of lymphokines on the activity of natural killer cells from endometriosis patients, with respect to the estradiol concentrations. Natural killer activity of peripheral blood was evaluated in 42 endometriosis patients who underwent laparoscopy for pelvic pain, infertility and benign adnexal masses, and it was correlated with serum estradiol levels. Twenty-five women with moderate and severe disease were re-evaluated for immune and endocrine parameters 4-8 weeks after surgery, before any specific adjuvant medical treatment, and analyzed for in vitro responsiveness of cytotoxic cells to interferon (IFN) alpha 2 beta and interleukin-2 (IL-2) incubation. Patients with moderate and severe endometriosis showed a significant decrease of natural cytotoxicity when compared with patients with mild and minimal disease (p = 0.01). The decrease of immune reactivity was independent of a reduced representation of natural killer cells, and persisted after surgical removal of all macroscopic endometriosis foci. A significant inverse relationship was observed between natural killer activity and serum estradiol levels, which resulted in moderate and severe disease (r = -0.4, p = 0.009) but not in stages I and II. The in vitro responsiveness of cytotoxic cells to lymphokine incubation was preserved; both IFN alpha 2 beta and IL-2 were able to increase the cytotoxicity of natural killer cells significantly from advanced-stage patients (p = 0.014 and p = 0.006 for IFN alpha 2 beta and IL-2 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Influence of neoadjuvant polychemotherapy on natural killer cell activity in patients with locally advanced cervical squamous carcinoma.

Peripheral blood natural killer (NK) cell activity against K562 tumor line was monitored in 16 patients with locally advanced squamous cervical carcinoma (II and III FIGO stages) during neoadjuvant polychemotherapy (cisplatin at 80 mg/m2 and bleomycin at 30 mg/m2). There was a significant progressive decrease in NK activity during the three cycles of antiblastic treatment (P = 0.008) without significant depletion of NK cell (CD56 and CD16 monoclonal antibody positive cell percentage and absolute number). A significant relationship was shown between basal NK activity levels and response to polychemotherapy; in fact, nonresponder patients had a significantly lower mean value of NK activity before polychemotherapy than responders (P = 0.044). In conclusion, NK activity declines as a result of antiblastic therapy; although polychemotherapy reduces tumor spread, its antineoplastic action may be affected by this decreased immune reactivity.

Adult↗