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Biomedical subjects

G Pettinato

Publications and source records attributed to G Pettinato.

At least 37 records · Page 2Linked to original sources

Measurement of neovascularization is an independent prognosticator of survival in node-negative breast cancer patients with long-term follow-up.

We measured neovascularization, epidermal growth factor receptor, and c-erbB-2 expression in a consecutive series of 233 surgically resected axillary lymph node-negative breast cancer patients with a long-term follow-up to define the usefulness of these parameters as independent prognostic indicators of overall survival (OAS). Microvessel count (MVC), as a measure of neovascularization, was determined using a monoclonal antibody against human factor VIII-related antigen. The median MVC of 20 (range, 4-76) was used as a cutoff value for discriminating between low and high vascularized tumors. Epidermal growth factor receptor and c-erbB-2 expression were evaluated by immunohistochemistry. Tumors were considered positive if >10% of the cells showed specific membrane staining. OAS curves were estimated by the Kaplan-Meier method. The independent prognostic effect of each variable was determined with the Cox proportional hazards model. High MVC (P = 0.04), high nuclear grade (P = 0.005), and high S-phase (P = 0.02) significantly affected OAS at univariate analysis. In a Cox multivariate analysis, the characteristics with an independent prognostic effect on OAS were: MVC (relative hazard, 2.12; 95% confidence interval, 1.18-3.81; P = 0.01) and nuclear grade (relative hazard, 2.83; 95% confidence interval, 1.12-7.17; P = 0.01). These results demonstrate that quantification of neovascularization adds useful independent prognostic information on survival in node-negative breast cancer patients with long-term follow-up.

Adult↗

The role of class I and class II HLA antigens in primary open angle glaucoma (POAG).

Several clinical and epidemiological studies have shown the role of genetic factors in the pathogenesis of primary open angle glaucoma (POAG). In this study, 30 patients affected by this disease were tissue-typed for HLA Class I and Class II antigens. The results pointed up an increased incidence of some antigens and, particularly, a statistically significant association with DQ1 and DR11 alleles.

Adult↗

Etoposide and idarubicin in a modified CHOP-like regimen (VICED) for aggressive non-Hodgkin's lymphomas.

The superiority of intensive versus standard chemotherapy for aggressive (I: intermediate; H: high grade) NHL is still debated; increased antitumor activity may be counterbalanced by increased toxicity. We have designed a first-line five-drug regimen (vincristine, idarubicin, cyclophosphamide, etoposide and deflazacort), with the aim of potentiating the CHOP protocol without losing tolerability and ease of administration. Seventy-one patients (33% aged > or = 65) entered the study. CR was obtained in 66.7% of patients (I: 74%; H: 56%), PR in 19.7%: overall response rate was 86.4%. Six patients were resistant, two died during treatment. With a median follow up of two years, relapse has occurred in 14 patients (8 I, 6 H). At 3 years, overall survival was projected to be 62.5% (I 73.5%; H 31.4%), disease free survival 66% (I 71%, H 56.3%). No organ toxicity occurred. Myelosuppression was moderate, with a nadir on the 14th day. Febrile episodes occurred in 16% of courses, dose delay in 19% of courses; dose reduction in 3% of patients. No patient required hospitalization. G-CSF was only occasionally used. This regimen has shown a potent antitumor effect with an excellent tolerance, even in elderly patients.

Adult↗

Renal failure from mitochondrial cytopathies.

Mitochondrial cytopathies are metabolic diseases, expressing mutations in nuclear DNA, punctiform mutations or depletions in mitochondrial DNA. These genetic lesions alter mitochondrial oxidative phosphorylation, with a reduction in energy produced for cell activity. Renal disease may be the first sign of mitochondrial cytopathy, or it may appear together with neurological and neuromuscular signs. Fanconi's syndrome, a benign sign of renal tubulopathy, is particularly frequent in newborns with mitochondrial cytopathy, whereas tubulointerstitial nephropathy, which affects infants and adults, is more serious because it develops into terminal uremia. Findings of hyperlactatemia and reduced enzymatic activity on the respiratory chain in tissue biopsies are of diagnostic significance in mitochondrial cytopathy. A breakthrough is being made in our understanding of genetic alterations in mitochondrial DNA, and with future therapy, the kidney, a target organ, may be safeguarded.

Adult↗

Differential immunohistochemical detection of transforming growth factor alpha, amphiregulin and CRIPTO in human normal and malignant breast tissues.

The expression of growth factors, such as transforming growth factor alpha (TGF alpha), amphiregulin (AR) and CRIPTO, a type-1 tyrosine-kinase growth factor receptor (erbB-2), and a tumor-suppressor gene (p53), that have been implicated in the development and/or the progression of breast cancer, was evaluated by immunohistochemistry in 100 human primary infiltrating breast carcinomas (IBC). AR and CRIPTO immunoreactivity was also assessed in 55 human breast ductal carcinomas in situ (DCIS). Within the 100 IBC, 80, 50, 73, 17, and 34 tumors expressed moderate to high levels of TGF alpha, AR, CRIPTO, erbB-2, and p53 respectively. In addition, AR and CRIPTO immunoreactivity were found in 11 and in 26 out of 55 DCIS respectively. In contrast, only 4, 3, and 2 out of 10 normal mammary-gland samples were weakly positive for TGF alpha, AR, and CRIPTO expression, respectively, whereas none was positive for erbB-2 or p53. Within the 100 IBC, expression of erbB-2 significantly correlated with high histologic and nuclear grading, with high growth fraction, and with estrogen-receptor (ER)- and progesterone-receptor (PgR)-negative tumors. A statistically significant correlation was also observed between p53 expression and high histologic grading, high growth fraction, and PgR-negative tumors. In contrast, no significant correlations were found between TGF alpha, AR, and CRIPTO immunoreactivity and various clinicopathological parameters, with the exception of a positive correlation between TGF alpha and ER expression. These data demonstrate that TGF alpha, AR, and CRIPTO expression are significantly increased in malignant mammary epithelium relative to normal epithelium. In particular, the differential expression of CRIPTO may serve as a potential tumor marker for breast carcinogenesis.

Adult↗

c-erbB-2 expression in FNAB smears and matched surgical specimens of breast cancer.

Most of the data regarding the significance of c-erbB-2 oncogene expression as a prognostic marker in breast cancer have been generated in many large retrospective studies by retrieving the corresponding oncoprotein in archival paraffin embedded sections. Recently, employing fresh breast cancer cells obtained by means of fine-needle aspiration biopsy, we found a rate of c-erbB-2 positive breast tumors (58%) higher than that reported in paraffin-embedded tissue sections by others studies. The present analysis was undertaken to investigate the impact of routine tissue processing on the preservation of the c-erbB-2 immunoreactivity. This issue was addressed by assessing the relative rate of c-erbB-2 oncoprotein immunodetection on FNAB smears and matched surgical specimens of breast cancer. The expression of c-erbB-2 oncoprotein was evaluated using the alkaline phosphate-anti-alkaline phosphatase (APAAP) technique in 54 breast aspirates and corresponding surgical specimens of primary breast cancer. Twenty-six (48%) smears and 23 (43%) matched paraffin sections gave specific signal for c-erbB-2 oncoprotein. The slightly higher incidence of c-erbB-2 expression found on smears seems to be mainly due to the better antigen preservation in the fresh cytological preparations. We conclude that routine histological processing may affect c-erbB-2 immunoreactivity; therefore, in mounting prospective studies, it is advisable to assess c-erbB-2 status in fresh tissue. Moreover, the assessment of c-erbB-2 expression on aspirate samples may yield additional information to the pre-surgical prognostic evaluation of breast cancer diagnosed by FNAB.

Biopsy, Needle↗

Selecting high-risk early breast cancer patients: what to add to the number of metastatic nodes?

High-risk early breast cancer patients are usually identified by the number of metastatic axillary nodes. To study whether other easily and inexpensively detectable morphological factors are able to detect high-risk patients, we performed a retrospective analysis of tumor size, and skin/fascia and nipple invasion. The data consisted of 941 node-positive cases registered between 1978 and 1991. Tumour size, and skin/fascia and nipple invasion were closely associated with the number of metastatic nodes (chi 2 test). The number of metastatic nodes, tumour size, skin/fascia and nipple invasion significantly affected disease free survival (DFS) and overall survival (OS) at univariate analysis. These results were confirmed by multivariate analysis with a model containing the number of metastatic nodes, tumour diameter categories, skin/fascia invasion, nipple invasion and adjuvant therapy as covariates: all variables significantly and independently affected risk of relapse and of death. All the variables studied were prognostic, within individual nodal categories, for both DFS and OS. In conclusion, the number of metastatic nodes is not the only prognostic tool with which to select high-risk patients for new intensive adjuvant programmes. Tumour size, and skin/fascia invasion or nipple invasion, taken singly or combined, are valuable prognostic factors that can identify patients with few metastatic nodes and poor outcome. On the basis of our data, we believe that a reconsideration of the pT4 category within the pTNM classification is in order, that is, chest wall invasion should be substituted by fascia invasion, and combined skin/fascia invasion could be a subcategory of each class defined by tumour size.

Adult↗

Endometriosis of the bowel with lymph node involvement. A report of three cases and review of the literature.

Three cases of endometriosis of the bowel with lymph node involvement were studied. Histologically, endometriotic glands with typical stroma were recognized throughout the intestinal wall, from the subserosal tissue to the mucosa. Foci of endometriosis were found in a number of pericolic lymph nodes occupying the subcapsular area or the cortex. The cytological smears were cellular, composed of large sheets of mucous columnar cells of intestinal origin, mixed with groups of recognizable endometrial cells and smaller spindly cells of endometrial stroma. Immunohistochemically, endometriotic cells showed positivity for cytokeratin and EMA, and they retained immunoreactivity for estrogen and progesteron in the intestinal lesions, as well as in the lymph nodes. Lymph nodal endometriosis was disclosed in two out of three cases only by multistep section examination of the pericolic lymph nodes, previously reported as negative for this feature.

Adult↗

A predictive index of axillary nodal involvement in operable breast cancer.

We investigated the association between pathological characteristics of primary breast cancer and degree of axillary nodal involvement and obtained a predictive index of the latter from the former. In 2076 cases, 17 histological features, including primary tumour and local invasion variables, were recorded. The whole sample was randomly split in a training (75% of cases) and a test sample. Simple and multiple correspondence analysis were used to select the variables to enter in a multinomial logit model to build an index predictive of the degree of nodal involvement. The response variable was axillary nodal status coded in four classes (N0, N1-3, N4-9, N > or = 10). The predictive index was then evaluated by testing goodness-of-fit and classification accuracy. Covariates significantly associated with nodal status were tumour size (P < 0.0001), tumour type (P < 0.0001), type of border (P = 0.048), multicentricity (P = 0.003), invasion of lymphatic and blood vessels (P < 0.0001) and nipple invasion (P = 0.006). Goodness-of-fit was validated by high concordance between observed and expected number of cases in each decile of predicted probability in both training and test samples. Classification accuracy analysis showed that true node-positive cases were well recognised (84.5%), but there was no clear distinction among the classes of node-positive cases. However, 10 year survival analysis showed a superimposible prognostic behaviour between predicted and observed nodal classes. Moreover, misclassified node-negative patients (i.e. those who are predicted positive) showed an outcome closer to patients with 1-3 metastatic nodes than to node-negative ones. In conclusion, the index cannot completely substitute for axillary node information, but it is a predictor of prognosis as accurate as nodal involvement and identifies a subgroup of node-negative patients with unfavourable prognosis.

Adult↗

An unusual, recurring breast tumor with features of eccrine spiradenoma: a case report.

A new case of breast tumor with features of eccrine spiradenoma is described. This neoplasm is exceedingly rare, because only two cases, arising in breast parenchima, have been previously reported. The patient was a 43-year-old woman and she experienced three local recurrences at 7, 20, and 30 months from the first excision. No distant metastases were observed. Microscopically, the tumor was circumscribed and showed a lobulated pattern. Neoplastic lobules consisted of packed, monotonous, basaloid epithelial cells with round to ovoid nuclei and scant cytoplasm. At the periphery, the lobules were delimitated by smaller cells with dark nuclei. Immunohistochemical reactivity in tumoral cells was found for both cytokeratin and epithelial membrane antigen; vimentin, muscle-specific actin, glial fibrillary acidic protein, S-100 protein, and carcinoembryonal antigen were all negative. Furthermore, the lesion showed a diffuse positivity for estrogen and progesterone receptors and a high growth fraction labelled by MIB-1 (Ki-67) antibody. These findings, in conjunction with the deep location of the tumor, suggest an origin of the neoplasm from the breast epithelium. Because of a potential local aggressive behavior, the excision of a wide rim of uninvolved breast tissue is recommended.

Adenoma, Sweat Gland↗

HLA typing and retinitis pigmentosa.

Retinitis pigmentosa is a disease whose pathogenesis remains largely obscure. A lot of evidences support the hypothesis that auto-immunity is involved, but no HLA antigen has ever been associated with retinitis pigmentosa. Ten patients with autosomal recessive retinitis pigmentosa were tissue typed for class I and II HLA antigens. The results of the study show a significant increase in the frequency of the antigens Cw4, Cw6 and DR11. High values of relative risk were found also for some class I antigens, but the size of the group of patients with these loci precluded a meaningful statistical analysis.

Adolescent↗

c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases.

PURPOSE: We studied retrospectively the interaction between c-erbB2 overexpression and adjuvant tomoxifen in node-negative breast cancer patients enrolled in the Gruppo Universitario Napoletano 1 (GUN-1) trial. PATIENTS AND METHODS: c-erbB2, evaluated by immunohistochemistry in 145 of 173 patients randomly assigned to 2-year adjuvant tamoxifen or no further therapy, was considered overexpressed if greater than 10% of the cells showed specific membrane staining. The role of each prognostic variable and their independent effect were studied using the Cox model. Disease-free (DFS) and overall (OAS) survival curves were estimated by the Kaplan-Meier method. RESULTS: As of November 30, 1994, the median follow-up period was 12 years. c-erbB2 was overexpressed in 43 of 145 patients (29.7%), which directly correlated with tumor size and inversely with estrogen receptor (ER) level. At univariate analysis, overexpression of c-erbB2 did not affect either DFS or OAS; tamoxifen had a greater effect on reducing the risk of recurrence than of death. Addition of c-erbB2 to a multivariate Cox model that contained menopausal status, tumor size, nuclear grade, and treatment as covariates did not affect the significance of the model for DSF or OAS, whereas addition of the first-order interaction between c-erbB2 and tamoxifen was statistically significant both for DFS and OAS. The same result was obtained when the model contained ER status and ER-tamoxifen interaction. Indeed, adjuvant tamoxifen significantly prolonged DFS and OAS in c-erbB2-negative cases, whereas it had no effect on DFS and OAS in c-erbB2-positive patients. CONCLUSION: In early-stage breast cancer patients, overexpression of c-erbB2 is a marker of lack of efficacy of adjuvant tamoxifen.

Adult↗

The prognostic value of lymphatic and blood vessel invasion in operable breast cancer.

BACKGROUND: This study assessed the prognostic effect of lymphatic and blood vessel invasion (LVI and BVI) on survival in a retrospective sample of 1408 patients with breast cancer. METHODS: Survival analysis was evaluated by univariate (Kaplan-Meier product limit method and log rank test) and multivariate (Cox model) analysis. Correlations among variables were studied by contingency tables and statistical significance was evaluated by chi-square test. RESULTS: Lymphatic vessel invasion was present in 34.2% of cases, and BVI in 4.2%. Lymphatic vessel invasion correlated with BVI (P < 0.0001), and both were correlated with metastatic axillary lymph nodes and increasing tumor size and grade; BVI was sporadic (only 10 cases) among lymph node negative patients. Although LVI was more frequent among premenopausal patients and those with ductal carcinomas, BVI was unrelated to menopausal status and tumor type. Lymphatic vessel invasion and BVI were associated with poor survival by univariate analysis (P < 0.0001). By multivariate analysis, relative risk of death was significantly increased when LVI was present both in the whole series as well as in the lymph node negative and lymph node positive subgroups; the prognostic role of LVI was independent of menopausal and lymph node status, tumor size, tumor grade, or adjuvant treatment. In the lymph node negative sample, LVI had strong prognostic power. In the lymph node positive sample, the prognostic role of LVI was also independent of the number of lymph nodes with metastases. Blood vessel invasion had no prognostic role in any subgroup. CONCLUSION: The prevalence of BVI was particularly low in this study, and the question of its possible prognostic role for patients with breast cancer should be assessed with methods that amplify its detection. LVI is a strong prognostic factor for operable patients with breast cancer. In lymph node negative patients, LVI is a predictor of poor prognosis for those who are consequently candidates for adjuvant therapy. Similarly, in lymph node positive patients, LVI is a predictor for a high risk of death for those who are candidates for highly intensive adjuvant strategies.

Adult↗

Gastric carcinoma with osteoclast-like giant cells. Report of four cases.

Four cases of gastric carcinoma are described that are associated with an osteoclast-like giant cell (OGC) stromal component. The patients were all middle-aged men (range 53-63 years). Microscopically, the tumors were characterized by a bland cytologic appearance, and an either solid or cribriform pattern. Osteoclast-like giant cells were found adjacent to, or intimately intermixed with, the neoplastic cells in the primary gastric masses and in the lymph nodal metastases and were often associated with lymphocytes, histiocytes, and desmoplastic stroma. By immunohistochemistry, mononuclear cells and OGCs showed diffuse positivity for alpha-1-antichymotrypsin, alpha-1-antitrypsin, and CD68. Neoplastic cells that were positive for keratin and CEA, also showed reactivity for vimentin and the latent membrane protein of Epstein-Barr virus in one case. At follow-up, three patients had died at 13, 15, and 24 months after diagnosis, and one is still alive, without evidence of disease, after 120 months. This report describes a novel variant of gastric carcinoma with distinctive and histologic features.

Carcinoma↗

Hemangiopericytoma: histopathological pattern or clinicopathologic entity?

The tumor designated by Stout and Murray as "hemangiopericytoma" (HPC) more than 50 years ago continues to represent a source of uncertainty and disagreement among pathologists. In particular, questions exist regarding the synonymity of a hemangiopericytomatous growth pattern--defined by a monomorphic population of compact polygonal or bluntly fusiform cells and a branching stromal vascular pattern with a "staghorn" configuration--and the presence of a reproducible biological entity. It has been shown repeatedly that these same histologic features may be observed at least focally in a diversity of neoplasms, including "true" hemangiopericytomas, synovial sarcomas, mesenchymal chondrosarcomas, infantile fibrosarcomas, malignant fibrous histiocytomas, malignant peripheral nerve sheath tumors, leiomyosarcomas, endometrial stromal sarcomas, solitary fibrous tumors, myofibromas, malignant mesotheliomas, thymomas, sarcomatoid carcinomas, malignant melanomas, and "phosphaturic mesenchymal tumors." Despite their potential sharing of the microscopic attributes in question, such neoplasms have individualistic clinical features and can also be distinguished from one another by specialized pathologic analyses. HPC is "defined" in that context by reactivity for vimentin, with or without CD34 and CD57, but it lacks other immunodeterminants of epithelial, neural, and myogenous differentiation. Paradoxically, this phenotype is indeed associated with the presence of myogenous-type cytoplasmic filaments in ultrastructural evaluations of HPC. Other lesions that may resemble "true" HPC--but which possess dissimilar subcellular and clinical characteristics--include solitary fibrous tumors, hemangiopericytomalike tumors of the sinonasal tract, and "infantile (congenital) hemangiopericytomas." Such observations suggest that the hemangiopericytoma is both a pathologic entity and a morphological pattern, and they emphasize the utility of adjuvant pathologic studies in this diagnostic context.

Actins↗

Pilomatrix carcinoma. A case report with immunohistochemical findings, flow cytometric comparison with benign pilomatrixoma and review of the literature.

We report a case of pilomatrix carcinoma in a 42 year old woman. The patient presented a rapidly growing 4-cm subcutaneous mass in the right preauricular area. She was free of recurrence 24 months after surgery. Immunoreactivity was studied for cytokeratins, epithelial membrane antigen, S-100 protein, blood group antigens, Leu-M1, beta-2-microglobulin, vimentin, neuron-specific-enolase and cellular binding for peanut agglutinin. Squamous cells were reactive for cytokeratin AE1/3, epithelial membrane antigen, blood group antigens B and H, and peanut agglutinin. Basaloid cells were focally reactive for cytokeratin AE1/3 and epithelial membrane antigen. Flow cytometry revealed a euploid DNA content and a high proliferative rate of the pilomatrix carcinoma and in benign pilomatrixoma studied for comparison. The pathological diagnosis must be based on histomorphological criteria.

Adult↗