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The objective of this study was to evaluate the prognostic significance of proliferating cell nuclear antigen (PCNA) immunoreactivity in tumor cells in patients with endometrial carcinoma. A population of 74 patients with FIGO stage I endometrioid adenocarcinoma of the endometrium, who underwent primary surgical management, were selected from January, 1986 to June, 1993 at the Department of Gynecologic and Obstetrics, Ancona University. The archival paraffin blocks from the uterine tumor specimens were recut and assessed for histologic re-examination and PCNA immunostaining (PC 10 monoclonal antibody; Dako, Denmark). A significant increase in PCNA index was observed with respect to nuclear grade (P < 0.001) and depth of myometrial invasion (P < 0.001), with the highest percentage values in nuclear grade 3 tumors and in ≥50% myometrial invasion. A PCNA index ≥50% was related significantly to disease-recurrence risk(P < 0.001) and PCNA index seems to be a significant prognostic parameter in stage I endometrial carcinoma, for disease-free survival. [ABSTRACT FROM AUTHOR]

Summary Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions.a2-Macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Becausea 2 (-macroglobulin has a binding affinity ()(K)d() for) zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35-60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2-IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented a 2 (-macroglobulin in the) circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin anda 2 (-macroglobulin ()(r)(= 0.75,)(P)(< 0.01,)(r)(= 0.78,)(P)(< 0.01, respectively) in cancer patients. In vitro zinc increases IL-2) production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase ina 2 (-macroglobulin,) which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency. [ABSTRACT FROM AUTHOR]

Background: The bcl-2 proto-oncogene codes for a protein which appears to block apoptosis. In our study, we examined bcl-2 protein expression in cervical squamous metaplasia, cervical intraepithelial neoplasia (CIN) and microinvasive squamous carcinoma with the aim of identifying a relationship between bcl-2 protein expression and neoplastic development and progression., Materials and Methods: Cervical bioptic samples were obtained from 86 white women, selected consecutively from our Colposcopic Service from January 1993 to June 1994, because of abnormal pap- smear suspicious for cervical dysplasia and/or human papilloma virus (HPV) infection. Upon histologic evaluation, 41 women had CIN, 23 cervical condyloma, and 22 squamous metaplasia. Ten patients with microinvasive squamous carcinoma, matched for age and demographic characteristics, were selected from our series of invasive cervical carcinomas and immunohistochemically analyzed. The expression of primary tumor bcl-2 protein was immunohistochemically evaluated by antihuman bcl-2 monoclonal antibody (diluted 1:100, Dako, Copenhagen, Denmark) on formalin-fixed paraffin-embedded tissue. Positive staining was expressed as a percentage of positive cells per 1000 counted dysplastic cells for each case., Results: Bcl-2 immunostaining was found in all the 22 squamous metaplasias, limited to the basal layer. Nineteen of the 41 CINs (46%) were bcl-2 immunoreactive, and 2 of the 10 microinvasive carcinomas (20%). By analysing CIN lesions, the bcl-2 protein showed a striking increase in the rate of positivity with increasing severity of CIN; the bcl-2 protein expression in CINs III was significantly higher than for CINs I, CINs II or microinvasive carcinomas (P = 0.03, P = 0.02, and P = 0.03 respectively). No relationship was observed between bcl-2 immunostaining and HPV infection. bcl-2 protein expression was not useful for predicting CIN I and II evolution, although the rate of persistence/progression was higher in bcl-2 positive dysplasias (7 of 9 cases, 78%) than in negative ones (13 of 21 cases, 62%) (p = 0.88)., Conclusions: Based on these results, it seems possible that the increase in bcl-2 expression in higher grade of CINs implies an increasing protection against programmed cell death, but also the induction of genetic instability in dysplastic epithelial cells and a greater capacity to evolve into invasive carcinoma.

Objective: The aim of our study was to investigate the expression of vascular endothelial growth factor (VEGF) by neoplastic cells in serous ovarian cystoadenocarcinomas; the correlation between this marker of angiogenesis, histopathologic parameters, disease-free survival, and MIB1 immunostaining was also evaluated., Materials and Methods: Thirty-two patients with serous ovarian cystoadenocarcinoma, treated at the Institute of Gynecology and Obstetrics, Ancona University (Italy), were used as study population; 10 women with serous cystoadenoma were also analyzed. The expression of VEGF was immunohistochemically evaluated by polyclonal antibody anti-VEGF (Santa Cruz, CA, dilution 1:100) on formalin-fixed paraffin-embedded tissue., Results: Compared to cystoadenomas, the tissutal VEGF immunostaining was significantly higher in cystoadenocarcinomas, with the highest values in architectural grade 3 neoplasms (P < 0. 001). A direct relationship was observed between VEGF immunostaining and MIB1 index (r = 0.44, P = 0.013). A relationship was defined between VEGF expression and disease-free survival, evaluated by Cox hazards analysis (P < 0.001)., Conclusions: Angiogenesis, evaluated by VEGF immunostaining, seems to be an interesting prognostic indicator in serous ovarian cystoadenocarcinoma, involved in neoplastic proliferation., (Copyright 1999 Academic Press.)

Background: Ras p21 expression seems to be associated with aggressiveness of neoplastic growth and metastatic potentially in human solid tumors. In our series of early-stage squamous cervical carcinoma, we evaluated ras p21 expression with respect to lymph nodal involvement; the aim was to analyse the ras p21 immunostaining as potential marker of lymphatic spread, and investigate the relationship between ras p21 expression and 72 kDa-metalloproteinase immunostaining., Patients and Methods: 46 patients with FIGO stage I squamous cell cervical carcinoma, who had undergone primary radical surgery with systematic pelvic and paraaortic lymphadenectomy (Piver's type III) at the Institute of Gynecologic and Obstetrics, Ancona University, were recruited from our series of 59 consecutive cases, and included the study. Any characteristic that could be relevant for prognosis was recorded such as: histologic grade of differentiation, tumor size, lymphatic spread, or adjuvant radiotherapy. Immunohistochemical staining was performed using the avidin-biotin peroxidase complex method (LSAB, Dako, Copenhagen, Denmark). Monoclonal antibody anti-pan ras (Ab-1) (Oncogene Science) and affinity purified rabbit anti-72 kDa-metalloproteinase antibody were used. Positivity for ras p21 was evaluated by semiquantitative analysis, while 72 kDa-metalloproteinase staining was expressed as the percentage of positive cells per 10(3) counted neoplastic cells (index)., Results: The expression of ras p21 was observed in 31 patients (67%) with FIGO stage I squamous cervical carcinoma. No connection was found between ras p21 expression and tumor size (P = 0.2), or histologic grade (P = 0.9), while a significant relationship was observed with respect to lymph nodal status (p = 0.048). By analysing 72 kDa-metalloproteinase immunostaining, ras p21 positive carcinomas showed significantly higher 72 kDa-metalloproteinase index than the negative ones (mean + standard deviation, 23.3% + 7.7% and 13.8% + 5.1% respectively, and P < 0.001)., Conclusions: Though the relatively small size of our series does not allow any definitive conclusion, a significant relationship between ras p21 expression and risk of lymphatic spread was detected in early-stage cervical carcinoma. ras p21 positivity seems to be an indicator of neoplastic aggressiveness and lymphatic spread, and is associated with significantly higher expression of 72 kDa-metalloproteinase.

Objective: In the present study, we assessed whether biologic characteristics of tumors in young patients differ from those observed in older patients with the same clinical and histologic characteristics, but ranging in age from 50 to 70 years. The hypothesis to be verified was whether cervical carcinoma in young patients presented an increased proliferative activity which might explain more aggressive behavior., Materials and Methods: Locally advanced cervical carcinoma tumor samples were obtained from our series of patients, maximum age 40 years, and 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 a percentage of positive cells per 10(3) counted neoplastic cells for each case. For each young patient, a control was selected among patients aged >/=50 years (range 50-70) matched for stage, tumor size, histologic type and grading, and lymphvascular invasion., Results: Fourteen of 73 patients (19.2%) with stage I and IIa cervical carcinoma who underwent primary radical surgery at our Institute between 1986 and 1994 were aged

We analyzed p53 immunoreactivity and clinical outcome in a series of cervical intraepithelial neoplasias (CIN), with respect to HPV DNA positivity. Cervical biopsy samples were obtained from 86 women who attended our Colposcopic Service from January 1993 to June 1994 due to abnormal pap-smear suspicious for CIN and/or human papillomavirus infection. Forty-one women with histologically confirmed CIN were included in the study. p53 positivity was immunohistochemically detected by monoclonal antibody anti-human p53 (pAb D0-7, Dako Denmark; dilution 1:50), and expressed as the percentage of positive cells. p53 positivity was observed in 78% of CIN lesions. In particular, all the HPV DNA-negative dysplasias expressed p53 protein while only 12 out of 21 (57%) HPV DNA-positive were p53 immunoreactive; (P = .003) the p53 immunostaining was also significantly higher in HPV DNA-negative than in positive CIN (P = .049). By analyzing p53 positivity with respect to clinical-pathologic evolution of the disease, among HPV DNA-negative cases, progressive dysplasia had significantly higher values of p53 immunostaining when compared to persistent and/or regressive lesions (P = .002). These findings imply that p53 immunostaining, when analyzed with respect to HPV DNA status, may help to understand the behavior of dysplastic lesions and define their therapeutic approach. Extensive p53 staining in HPV DNA-negative CIN is probably correlated with a high risk of progression.