Biomedical subjects

J C Felix

Publications and source records attributed to J C Felix.

At least 19 recordsLinked to original sources

PubMed2005

Menstrual-like breakdown and apoptosis in human endometrial explants.

BACKGROUND: Apoptosis occurs in late secretory and menstrual human endometrium and is thought to play an important role in endometrial physiology. Menstrual-like breakdown has been observed in vitro in endometrial explants. The purpose of this study was to assess the role of apoptosis in menstrual-like breakdown in human endometrial explants. METHODS: Human endometrial tissue was obtained during the mid-secretory phase and cultured with or without estrogen and progesterone. The occurrence of breakdown was assessed by histology. Apoptosis was determined by gel electrophoresis for the detection of DNA fragmentation and by immunohistochemistry using the M30 CytoDEATH and anti-cleaved caspase-3 (CASP3) antibodies for the detection of caspase activity. Expression of BCL2 and BAX was quantified using real-time PCR analysis. RESULTS: Apoptosis occurred in human endometrial explants at all time-points studied. Cleaved CASP3 and M30 antigen expression increased in all explants, suggesting the involvement of CASP3 in the apoptosis. Low BCL2:BAX ratios were observed in all samples when compared with pre-culture controls. Estradiol and progesterone supplementation of the culture media reduced or eliminated menstrual-like breakdown but did not affect the degree of apoptosis observed. CONCLUSIONS: The apoptosis observed in endometrium during the late secretory phase and menstrual phase does not appear to be mechanistically related to the tissue breakdown but rather may be involved in the impending remodelling that occurs in the endometrium in the transition from secretory to proliferative phase following the menses.

Adult↗

PubMed2005

Digital camera assessment for detection of cervical intraepithelial neoplasia in rural El Salvador.

OBJECTIVE: To explore the feasibility of digital photography for primary cervical cancer screening in a low-resource setting in El Salvador. METHODS: Three independent examiners performed Pap test, visual inspection, digital camera assessment and colposcopy on each subject. RESULTS: Lesions were detected in 99 of 504 patients (20%) by visual inspection, 72/504 (14%) by DART and 90/504 (18%) by colposcopic impression. Seven of 504 patients (1.3%) had CIN on histology. Pap detected 2 of 7 subjects (29% sensitivity) (C.I. 4%, 56%), visual inspection detected 5 of 7 (71% sensitivity, C.I. 34%, 95%), digital assessment detected 6 of 7 (86% sensitivity C. I. 45%, 99%), and colposcopic impression detected 5 of 7 (71% sensitivity, C.I. 34%, 95%). CONCLUSION: This small pilot trial demonstrates the potential value and feasibility of performing digital camera assessment of the reproductive tract on women in a developing country setting.

Adult↗

PubMed2001

Immunohistochemical expression of cell cycle proteins E2F-1, Cdk-2, Cyclin E, p27(kip1), and Ki-67 in normal placenta and gestational trophoblastic disease.

The role of cell cycle protein expression in gestational trophoblastic disease is poorly understood. In this study we investigated the immunostaining patterns of G(1) restriction point and G(1)-S regulatory proteins E2F-1, Cdk2, cyclin E, p27(kip1), and the proliferation marker Ki-67 on routinely processed sections of 29 hydatidiform moles (10 partial moles and 19 complete moles, including 9 persistent moles), 7 choriocarcinomas, and 7 normal placentas. Ki-67 trophoblast staining decreased with increasing gestational age of the placenta, and showed maximal expression in gestational trophoblastic disease. Cyclin-dependent kinase activity, as reflected by Cdk2 expression patterns, also decreased with placental maturation. E2F-1 was uniquely expressed by trophoblasts of moles and choriocarcinoma. Cyclin E was maximally expressed by complete moles and choriocarcinomas, and showed an inverse relationship with the cyclin-dependent kinase inhibitor p27(kip1). Abnormal trophoblastic proliferations may be mediated through interactions of Cdk-2, E2F-1, cyclin E, and p27(kip1). Overexpression of cyclin E was associated with more aggressive forms of gestational trophoblastic disease. However, we did not find distinguishing features between complete moles that spontaneously resolved after evacuation and persistent moles that required chemotherapy. The different expression patterns of cyclin E and E2F-1 in partial and complete moles may be useful in distinguishing these two entities. Furthermore, loss of p27(kip1) in malignant trophoblast may represent a necessary step in the development of choriocarcinoma.

CDC2-CDC28 Kinases↗

PubMed2001

Expression of human telomerase reverse transcriptase, the catalytic subunit of telomerase, is associated with the development of persistent disease in complete hydatidiform moles.

OBJECTIVE: This study was undertaken to determine the putative role of telomerase activity and human telomerase reverse transcriptase (hTERT) expression in the development of persistent disease in patients with a diagnosis of complete hydatidiform mole. The ribonucleoprotein telomerase has been shown to have a major role in the process of cellular immortality and carcinogenesis. The reactivation of this enzyme that occurs in the development of malignancies appears to be limited by the regulation of its catalytic subunit hTERT. Compared with their somatic counterparts, most human malignancies demonstrate telomerase activity, and this activity is dependent on the cellular presence of hTERT. The role of telomerase in the pathogenesis of complete hydatidiform moles is not clearly understood. Moreover, the role of hTERT in trophoblastic disease, as well as in the development of persistent trophoblastic disease, has yet to be elucidated. STUDY DESIGN: Telomerase activity and hTERT expression were analyzed in the initial uterine evacuation specimen of 54 complete hydatidiform moles by use of the telomeric repeat amplification protocol assay and reverse transcription-polymerase chain reaction methods. The results were compared and then correlated with the development of persistent trophoblastic disease. RESULTS: Among the 54 patients who were examined with a diagnosis of complete hydatidiform mole, persistent trophoblastic disease requiring postevacuation chemotherapy developed in 6. In the remaining 48 patients, spontaneous remission of the disease occurred after uterine evacuation. Both telomerase activity and hTERT expression were detected in all 6 cases of persistent disease on the initial molar tissue sampled. Among the 48 nonpersistent moles, telomerase activity was detected in 29 (60%) and hTERT expression was demonstrated in 26 (54%). The detection of hTERT expression was significantly associated with the presence of persistent disease (P =.035). Moreover, the absence of hTERT expression in molar tissue obtained from uterine evacuation demonstrated a 100% negative predictability in determining cases of complete mole that were nonpersistent. CONCLUSIONS: Compared with telomerase activity, the expression of hTERT is significantly associated with the development of persistent disease in complete hydatidiform moles. The absence of hTERT expression in the initial tissue sample from complete moles may have potential clinical value in determining patients who will eventually undergo spontaneous remission after uterine evacuation.

Adolescent↗

PubMed2001

Micronized progesterone regulation of the endometrial glandular cycling pool.

We sought to determine if micronized progesterone in estrogen-primed women has an effect on the available cycling pool of proliferating glandular cells by studying 107 postmenopausal women who participated in a double-blind cyclical HRT trial. Each received 0.625 mg/day of conjugated equine estrogen (Premarin) orally for 6 weeks (cycle 1), followed by a baseline endometrial biopsy. These women were randomized to one of four doses (100 through 400 mg/day) of progesterone taken the last 10 days of each cycle or to estrogen only. Cyclical HRT (25-day cycles) was continued for three more cycles. Endometrial biopsies were performed at the end of cycle 4 and 64 subjects demonstrated an adequate biopsy for immunohistochemical evaluation. The number of proliferating gland cells was determined by an immunohistochemical stain measuring positive MIB1 staining nuclei per thousand gland cells. The number of proliferating endometrial gland cells in the cycling pool of women receiving 300- and 400-mg daily doses of progesterone was low (mean 4.9 and 1.7, respectively) when compared with women receiving 100 mg progesterone (mean 27.0) or to unopposed estrogen (mean 30.3). Late secretory endometrium from 19 premenopausal women had a mean of 0.6. In the progesterone-treated subjects, biopsies showed that secretory maturation increased as the serum progesterone and doses of progesterone increased. We conclude that micronized progesterone given to estrogen-primed menopausal women results in a dose dependent decrease in endometrial gland proliferation. The use of an immunohistochemical stain and the diagnosis of histologic secretory maturation are complementary techniques in determining the inhibition of glandular proliferation.

Antigens, Nuclear↗

PubMed2000

Ovarian epithelial tumor growth promotion by follicle-stimulating hormone and inhibition of the effect by luteinizing hormone.

OBJECTIVES: The role of gonadotropins in ovarian epithelial cancer development is still controversial. Follicle-stimulating hormone receptor (FSHR) status in ovarian epithelial tumors (OETs) and their presumed precursor lesions has never been studied in detail. The objective of this study was to examine whether FSHR is expressed in OETs and to investigate the possible different roles of the gonadotropins in ovarian cancer development. METHODS: Twenty ovarian epithelial inclusions (entrapments or invaginations of ovarian surface epithelium) from benign ovaries and 60 OETs including 12 cystadenomas, 18 borderline tumors, and 30 carcinomas were examined for FSHR expression by using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization (ISH), and immunohistochemistry (IHC). We also studied the mitogenic activity of FSH on two FSH and luteinizing hormone (LH) receptor-positive ovarian epithelial carcinoma cell lines (AO and 3AO) and on the modifying effect of LH on this activity. Growth-stimulating effects of the gonadotropins were tested in vitro with measurement of cell numbers, S-phase by flow cytometry, and changes in the cellular proliferative marker Ki-67. RESULTS: Positive FSHR mRNA expression by RT-PCR (the most sensitive method) was found in 100% of epithelial inclusions, 100% of cystadenomas, 94% of borderline tumors, and 60% of carcinomas. There was a nonstatistically significant trend of decreasing positivity with increasing carcinoma grade. ISH and IHC gave similar, but somewhat less sensitive, results. A dose-response effect was seen with FSH, with a 1.6-fold increase in cell numbers with a maximally stimulating FSH concentration of 40 IU/L for a period of 48 h. These proliferative cellular effects were not observed when the cells were stimulated by LH in the range 1 to 100 IU/L. Most significantly, the growth stimulating effects of FSH could be blocked by the simultaneous administration of LH. CONCLUSIONS: FSHR is present in the majority of ovarian epithelial inclusions and OETs. The steady decline of FSHR expression from benign cystadenoma to borderline tumor to carcinoma suggests that FSH may be needed in early ovarian cancer development. Gonadotropins, FSH and LH, may have different roles in ovarian cancer cell proliferation. FSH, not LH, may be an important ovarian epithelial cell growth-promoting factor. The "opposing" effect of LH on FSH stimulation may explain why high FSH levels at postmenopausal ages are not associated with great increases in ovarian cancer risk.

Adult↗

PubMed2000

Apoptosis may be an early event of progestin therapy for endometrial hyperplasia.

OBJECTIVE: The aim of this study was to investigate the role of apoptosis during progestin therapy for the treatment of endometrial hyperplasia. METHODS: Pre- and posttreatment paraffin-embedded endometrial tissue samples from 19 women with endometrial hyperplasia were examined for changes in glandular cellularity and apoptotic activity related to the administration of progestins. Twelve patients were successfully treated with progestin therapy and 7 patients failed treatment. Glandular cellularity was assessed based on calculating the average number of cells per gland obtained on histologic examination of hematoxylin and eosin stained tissue sections. Apoptotic activity was assessed on the same tissue sections by counting the average number of apoptotic cells per 10 high power fields (hpf) using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. The effects of progesterone on apoptotic activity in a low-grade endometrial adenocarcinoma cell line (Ishikawa cells) was also examined using an ELISA cell death detection kit. RESULTS: Glandular cellularity significantly decreased with progestin therapy in both treatment outcome groups. The reduction in cells per gland was significantly greater in the group of successfully treated cases compared to the treatment failures (P = 0.005). However, within the successfully treated group, in situ detection of apoptotic cells using the TUNEL assay showed no statistical difference between pre- and posttreatment endometrial samples. Interestingly, a significant decrease in apoptosis was found in posttreatment samples of the group with persistent hyperplasia. The average number of apoptotic cells detected in 10 hpf was reduced from 7.9 prior to treatment to 3.1 after progestin therapy (P = 0.03). In the progesterone-treated Ishikawa cell line, an increase in apoptotic activity started at 24 h, reached a peak at 48 h, and continued up to 72 h of hormone treatment. At 48 h, apoptotic activity was 42.6% greater than in the untreated control (P = 0.04). By 72 h of progesterone treatment, apoptosis was 37.2% greater in the treated cells compared to the noninoculated cells (P = 0.04). CONCLUSIONS: Progestin-induced apoptosis may occur during the early period of treatment for endometrial hyperplasia. Compared to the fully responsive group, persistent endometrial hyperplasia may have intrinsically different molecular mechanisms in response to progestin therapy.

Adult↗

PubMed2000

The relationship of inflammation in the papanicolaou smear to Chlamydia trachomatis infection in a high-risk population.

Chlamydia trachomatis is a significant etiologic agent responsible for pelvic inflammatory disease leading to tubal infertility. A screening test aimed at identifying women at risk for Chlamydia trachomatis would be of great utility. The Papanicolaou smear is the most widely used screening test in the world. The association of inflammatory cells in the Papanicolaou smear to Chlamydia infection is controversial. We retrospectively examined the Papanicolaou smears of 80 Chlamydia-negative patients with 80 age-matched Chlamydia-positive patients in a high-risk population to see if a significant difference in inflammation was noted between the two groups. We found a statistically significant difference in inflammation scores between the Chlamydia-positive and Chlamydia-negative groups, evidenced by a sensitivity of 83% and a positive predictive value of 65% when using inflammation on Papanicolaou smears as a marker for Chlamydia infection. Grading of inflammation in the Papanicolaou smear can be of potential use in defining patients at highest risk for Chlamydia in a group considered to be at high risk based on sexual history.

Adult↗

PubMed1999

A single-visit cervical carcinoma prevention program offered at an inner city church: A pilot project.

BACKGROUND: A single-visit cervical carcinoma prevention program was implemented, integrating screening, diagnosis, treatment, and health education in the familiar environment of the community church. METHODS: Nonpregnant women age 18 years or older, who had not received cervical carcinoma screening in the preceding year were eligible. Subjects provided information on personal demographics, health, and knowledge regarding cervical carcinoma prevention. Thereafter, cervical cytology was collected, processed, and interpreted on site. Participants attended small-group instruction on cervical carcinoma prevention. Screening results were given to each subject individually. Patients with abnormal cytology underwent immediate colposcopy with biopsies or loop electrosurgical excision procedure as indicated. Participant satisfaction and educational impact were evaluated. RESULTS: Ninety of the 98 participants reported that Spanish was their native language; 59 did not speak English. Fifty-four had had fewer than 6 years of education and 55 were unemployed. Seventy-eight did not have a regular physician or health insurance. Twenty-four either had never undergone cervical carcinoma screening or had let more than 5 years elapse since their previous examination. None of nine potential barriers assessed correlated with past compliance with cervical carcinoma screening. The mean time for processing and on-site interpretation of cervical cytology smears was 22.6 +/- 5.3 minutes. The median time patients spent in the program was 75 minutes. There was a significant improvement in the subjects' knowledge regarding cervical carcinoma prevention. All participants were highly satisfied. CONCLUSIONS: This parish-based, integrated, single-visit program for the prevention of cervical carcinoma was easily implemented and provided care to a substantial proportion of underserved patients.

Adult↗

PubMed1999

Differences in p16 gene methylation and expression in benign and malignant ovarian tumors.

OBJECTIVE: The aim of this study was to test the hypothesis that DNA methylation is important for silencing the p16 tumor suppressor gene in ovarian epithelial tumors and to compare the prevalence of this mechanism among different ovarian epithelial tumor subtypes. METHOD: Methylation-specific PCR was used to analyze the p16 gene for DNA methylation in 20 ovarian cystadenomas, 15 low malignant potential (LMP) tumors, and 37 carcinomas. p16 expression was determined immunohistochemically in 58 of these tumors (16 cystadenomas, 13 LMP tumors, 29 carcinomas). Differences in methylation or expression rates between specific tumor subgroups were examined by Fisher's exact test. RESULTS: Fragments from the distal promoter and beginning of the first exon of the p16 gene were both methylated in 5 of 15 (33%) LMP tumors compared to 2 of 37 (5%) carcinomas (P = 0. 02). Those sites were also methylated in 5 of 20 (25%) cystadenomas. Lack of p16 expression was present in 7 of 16 cystadenomas, 4 of 13 LMP tumors, and 22 of 29 carcinomas (P [LMPs versus carcinomas] = 0. 01) and correlated with methylation changes in LMP tumors (P = 0.05). p16 expression was correlated with mucinous differentiation in cystadenomas (P = 0.001). CONCLUSION: p16 silencing may be important for the development of ovarian carcinomas and a subset of LMP tumors. Changes in DNA methylation may be more important for inactivation of this gene (and perhaps other tumor suppressor genes) in LMP tumors, which lack many of the alternative mechanisms present in carcinomas. p16 expression is primarily related to mucinous differentiation in cystadenomas.

Carcinoma↗

PubMed1999

Down-regulation of bcl-2 is a potential marker of the efficacy of progestin therapy in the treatment of endometrial hyperplasia.

OBJECTIVE: The objective of this study was to evaluate the expression of bcl-2, a regulatory protein in programmed cell death, in endometrial hyperplasia before and after progestational therapy. METHODS: Pre- and posttreatment paraffin-embedded endometrial tissue samples from 20 women with an initial diagnosis of endometrial hyperplasia were obtained from archived files. Cases were evaluated and classified as either complete resolution of hyperplasia or persistent hyperplasia in response to progestin treatment. Sections were examined for bcl-2, estrogen receptor, and progesterone receptor expression using immunohistochemistry and compared within the treatment response groups. RESULTS: Among the 20 women studied, 13 had complete regression of their hyperplasia with progestin treatment and 7 had evidence of persistent disease after therapy. Bcl-2 expression was significantly decreased after treatment from a mean reactivity score of 2.08 to 0.31 (P = 0.0005) in the group of patients whose hyperplasia completely regressed with progestin administration. Among the women who had persistent hyperplasia after therapy, no significant change was observed between pre- and posttreatment bcl-2 expression, with a mean reactivity of 1.86 to 1. 29, respectively (P = 0.075). Progestational therapy significantly decreased the status of estrogen receptors from a mean score of 2.08 to 0.46 (P = 0.0005) in completely resolved cases of hyperplasia and from 2.00 to 0.43 (P = 0.0025) in persistent hyperplasias. Treatment also significantly decreased the status of progesterone receptors from a mean reactivity score of 1.92 to 0.31 (P = 0.0005) in cases of regressed hyperplasia and from a mean reactivity of 1.86 to 0.29 (P = 0.005) in persistent cases of hyperplasia. CONCLUSIONS: Bcl-2 expression decreases following successful progestin treatment of endometrial hyperplasias, whereas it remains expressed in hyperplasias which persist despite progestational therapy. This suggests that bcl-2 expression may represent a component of the therapeutic effects exerted in the endometium during progestational therapy in the treatment of hyperplasia. The activity of the oncoprotein may be a potential measure of the progress of treatment.

Adult↗

PubMed1999

Cold-knife conization versus conization by the loop electrosurgical excision procedure: a randomized, prospective study.

OBJECTIVE: Our purpose was to compare the diagnostic ability and treatment efficacy of conization by the loop electrosurgical excision procedure with cold-knife conization. STUDY DESIGN: One hundred eighty women who required conization for diagnosis and treatment of cervical dysplasia or microinvasive cervical carcinoma were prospectively enrolled in a randomized clinical trial to receive either cold-knife conization or conization by the loop electrosurgical excision procedure. Conization complications, rate of lesion clearance, and therapeutic outcome were assessed for the 2 study groups. RESULTS: There were no statistically significant differences in the complication rate (P = 1.00), the rate of lesion clearance (P =.18), or the rate of disease recurrence (P =.13) between the 2 study groups. The mean follow-up was 11.2 months in the cold-knife conization group and 10.4 months in the loop-excision conization group. CONCLUSION: Cold-knife conization and loop-excision conization yield similar diagnostic and therapeutic results.

Adenocarcinoma↗

PubMed1999

p53 mutations and expression in ovarian cancers: correlation with overall survival.

The p53 gene is altered in approximately 50% of all human malignancies. p53 overexpression, identified by immunohistochemistry, and p53 mutations, identified by single-strand conformational polymorphism (SSCP) and DNA sequencing, have been described in ovarian cancers. p53 overexpression has been correlated with poor outcome for women with ovarian cancer in some studies. With only limited data, the assumption has been made that p53 overexpression corresponds to p53 mutations. The purpose of this investigation was to assess p53 alterations in ovarian cancer to determine if p53 overexpression corresponds with mutations in the p53 gene, and to assess whether either predicts clinical outcome in ovarian carcinoma. Frozen ovarian carcinoma tumor specimens from 105 patients were analyzed by immunohistochemical staining for p53 expression. SSCP was used to screen for mutations and DNA sequencing was used to confirm the specific mutation in exons 2 to 11, encompassing the entire p53 open reading frame. Those ovarian carcinomas identified as wild-type p53 by SSCP were subjected to automated DNA sequence analysis of the entire open reading frame. Relative to DNA sequence analysis, the sensitivity of SSCP was 85% and the specificity was 98%. Immunohistochemical staining demonstrated that 72 of the 105 (69%) cases had positive immunostaining. SSCP and DNA sequencing identified and confirmed mutations in 60 of the 105 carcinomas (57%). Although there was a statistically significant association between p53 immunostaining and p53 mutations (p = 0.0002), false-negative and -positive results were identified. Tumor grade (p = 0.03), stage (p = 0.08), and overall survival (p = 0.15) were moderately associated with positive p53 immunostaining. Patients with p53 mutations and overexpression had shorter overall patient survival (p = 0.02). The findings demonstrated that, individually, p53 mutations and p53 overexpression were each related to shorter patient survival, but the strongest predictor of outcome was a combination of both mutations and overexpression. Comparisons of overall survival for women with mutations in loop 2, loop 3, and the loop-sheet-helix domains together showed a statistically significant difference in survival compared to survival of women whose ovarian cancers had other mutations (p = 0.046).

Adult↗

PubMed1998

Influence of quantity of lymph-vascular space invasion on the risk of nodal metastases in women with early-stage squamous cancer of the cervix.

OBJECTIVE: To determine if the quantity of lymph-vascular space invasion influences the risk of pelvic nodal metastases in women with early-stage cervical squamous carcinoma. METHODS: Between 1991 and 1997, 105 women with stages IA2, Ib, and IIa squamous carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy. The histopathology slides were prospectively reviewed. If lymph-vascular space invasion (LVSI) was present, the amount was quantified in four ways: percentage of cervical histopathologic sections containing LVSI, percentage of sections with tumor containing LVSI, total number of foci of LVSI, and maximal number of foci of LVSI in 10 high-powered fields. These measures of LVSI were correlated with the risk of nodal metastases. RESULTS: Seventy-three (70%) women had tumors with LVSI. Of these, 23 had pelvic nodal metastases. All women with nodal metastases had tumors with LVSI. Using logistic regession, independent predictors of nodal metastases were depth of cervical stromal invasion (P = 0.01) and tumor size (P = 0.04). LVSI was also a significant predictor of nodal metastases based on the Mantel-Haenszel test (P = 0.01). In women whose tumors contained LVSI, logistic regression identified tumor size (P = 0.004) and LVSI in > 45% of all cervical histopathologic sections (P = 0.002) as significant predictors of nodal metastases. CONCLUSION: The quantity of LVSI, as defined by the percentage of all cervical histopathologic sections containing LVSI, correlates significantly with the risk of nodal metastases in women with early-stage squamous carcinoma of the cervix.

Adult↗

PubMed1998

Imbalanced expression of inhibin and activin subunits in primary epithelial ovarian cancer.

OBJECTIVES: Inhibins and activins are related gonadal peptides with opposing biologic actions on gonadotropin regulation, cell differentiation, and proliferation. The previous study of activin in ovarian cancer cell lines suggests that activin may promote growth of ovarian cancer. Elevated serum inhibin levels were also found in ovarian cancer patients; however, the source of elevated inhibin is unknown. This study is designed to examine the expression of inhibin and activin subunits as well as activin receptor in primary ovarian epithelial tumors to explore their role in the process of ovarian epithelial tumorigenesis. METHODS: The protein and mRNA expression of alpha and betaA subunits of inhibin/activin as well as of activin receptor mRNA were examined with immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in 112 ovarian carcinomas. Cases included 59 serous, 23 endometrioid, 16 mucinous, 9 clear cell, and 5 undifferentiated carcinomas. We also tested normal ovary and benign and borderline ovarian tumors for comparison. These included 17 ovarian surface epithelial samples, 6 serous and 5 mucinous cystadenomas, and 9 serous and 7 mucinous tumors of low malignant potential. A total of 139 ovarian tumors were analyzed by IHC and a total of 63 ovarian tumor samples were tested by RT-PCR. RESULTS: Inhibin alpha subunit expression was found in 47% of ovarian surface epithelia and focal alpha immunoreactivity was seen in tumor stroma, but was not found in the epithelial component of ovarian cystadenomas, tumors of low malignant potential (LMP), or carcinomas. Activin betaA subunit was expressed in 93% of surface epithelia, in the epithelial component of all cystadenomas, in 81% of LMP tumors, and in 72% of carcinomas, but not in tumor stroma. Activin expression did not correlate with histologic grades, tumor types, and surgical stages. Activin receptor type I and II mRNA-amplified products were found in virtually all the surface epithelial samples and ovarian tumors. CONCLUSIONS: The data suggest that imbalanced expression of inhibin and activin subunits in ovarian surface epithelium may represent an early event which leads to epithelial proliferation. Unopposed betaA and activin receptor expression in epithelial compartment of ovarian tumors suggest that activin may be available as autocrine and/or paracrine factors in ovarian epithelial tumors. But exact roles of inhibin and activin in ovarian epithelial tumors remain to be defined.

Activin Receptors↗

PubMed1998

The effects of progesterone and progestins on endometrial proliferation.

A total of 99 premenopausal and 27 postmenopausal women were evaluated to determine the quantity of glandular proliferation resulting from progestin inhibition of estrogen-primed subjects and of subjects without hormonal stimulation. Endometrial glandular proliferation rates were determined by using mitosis counts, proliferating-cell nuclear antigen (PCNA), and nuclear cyclin (MIB1) immunocytological staining. The endometria of normally cycling premenopausal women, of women who received a synthetic progestin, and of untreated postmenopausal women were studied. In untreated normally cycling premenopausal women, the proliferation of the glandular epithelium was increased during the follicular phase and decreased during the luteal phase. Premenopausal women receiving a synthetic progestin and untreated postmenopausal women who were not estrogen-primed showed minimal epithelial proliferation. Endometrial glandular proliferation is inhibited by endogenous progesterone in premenopausal women. Endometrial proliferation is markedly reduced in premenopausal women receiving a synthetic progestin and in untreated postmenopausal women.

Atrophy↗

PubMed1998

p53 immunostaining as a significant adjunct diagnostic method for uterine surface carcinoma: precursor of uterine papillary serous carcinoma.

Uterine papillary serous carcinoma (UPSC) is a biologically aggressive carcinoma that causes a disproportionate number of endometrial cancer deaths because of its dismal clinical outcome. Although the precursor lesion of UPSC has been suggested both morphologically and molecularly, diagnosis continues to represent a challenge to surgical pathologists, particularly in biopsy specimens, largely in part because of its multiple histologic patterns and many benign morphologic mimics. In this study, we used p53 immunohistochemical staining as an adjunct test to correctly identify six cases of uterine surface carcinoma (USC) prospectively and three cases retrospectively. Both sensitivity and specificity for this immunostaining method approached 100% when the cutoff score of p53 overexpression was 7 or higher. The precision estimated by receiving operating characteristic curve was 100%, indicating that the diagnostic value of the score for p53 overexpression was very high. p53 immunohistochemical staining was considered a significant adjunct diagnostic method for the probable precursor lesion of UPSC. The probable precursor lesion of UPSC, previously referred to as endometrial intraepithelial carcinoma or endometrial carcinoma in situ, appears to represent the early phase of UPSC. However, unlike its names would suggest, this lesion is often multicentric and behaves in a more aggressive fashion than regular in situ carcinomas. For this reason, we prefer the term uterine surface carcinoma, a term that is more descriptive and less restrictive, to emphasize the unique aggressive nature of the UPSC precursor lesion. The reason we postulate using the term uterine surface carcinoma rather than endometrial intraepithelial carcinoma or endometrial carcinoma in situ is that the latter terms would seem define a neoplastic process confined to the endometrial epithelium without potential for metastasis. In reality, the precursor lesion of UPSC has a tendency to stromal and vascular space involvement as seen by the presence of stromal and vascular invasion in one of the prospectively identified USC cases. Therefore, the term uterine surface carcinoma is selected to alert clinicians that this early carcinoma has features of carcinoma in situ, but still carries a potential for metastasis.

Aged↗

PubMed1997

Detection of hyperdiploid malignant cells in body cavity effusions by fluoresence in situ hybridization on ThinPrep slides.

BACKGROUND: Benign body cavity effusions sometimes cannot be distinguished from malignant ones by conventional cytology. The authors performed fluorescence in situ hybridization (FISH) on ThinPrep slides using chromosome specific probes to see if hyperdiploid malignant cells could be detected in 20 body cavity effusions. The results were then compared with those of conventional cytology. METHODS: A total of 20 body cavity effusions from 19 patients were studied using conventional cytology and FISH. Probes specific for chromosomes 3, 8, 10, and 12 were used to detect hyperdiploidy on ThinPrep slides (Cytyc Corporation, Boxborough, MA). RESULTS: A total of 13 patients had malignant conditions (either prior history of malignancy or the presence of malignancy anywhere in the body). Conventional cytology and FISH were both positive in 5 of these patients (6 samples) and negative in 2 patients. The results for one sample were inconclusive by both methods. There were 5 discrepant cytology-FISH results in patients with malignant conditions. One sample was positive by FISH and negative by cytology, one was positive by FISH and "atypical" by cytology, and three were inconclusive by FISH and negative by cytology. FISH results were either negative (in 4 samples) or inconclusive (in 2 samples) in the 6 patients with benign conditions. CONCLUSIONS: FISH can detect hyperdiploid malignant cells in body cavity effusions and is especially useful when the major cell population consists of malignant cells that cannot be differentiated from mesothelial or "atypical" cells. It is less useful in detecting a small population of malignant cells hidden in an inflammatory or reactive cell background. More studies are needed to establish diagnostic criteria further and to assess the clinical usefulness of this procedure.

Adult↗