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Purpose: Tumors with p53 overexpression have been associated with enhanced resistance to cisplatin-based chemotherapy in a few and small studies involving non-small cell lung cancer. The relationships and interactions between p53, Rb and bcl-2 immunostaining, clinical parameters and response to cisplatin-based chemotherapy were evaluated in the present study. Experimental design: Histological specimens obtained by bronchial or fine-needle biopsy from patients who underwent cisplatin-based chemotherapy between 1992 and 1999 were evaluated by immunostaining. Results: There were 102 patients, 88 men. Median age was 63 years; 47 had stage III and 55 stage IV disease. Forty-six tumor samples (45%) had positive immunostaining for p53, 61 (59%) had negative immunostaining for Rb and 8 (8%) had positive immunostaining for bcl-2. The response rate of the group with p53 positive immunostaining was 26% versus 57% of the p53 negative group ( P =0.004). In multivariate analyses p53 positive immunostaining was identified as an independent predictive factor for resistance to cisplatin-based chemotherapy ( P =0.006). Conclusions: Our study confirmed an association of p53 immunostaining and response rate of patients treated with cisplatin-based chemotherapy.

DNA ploidy image analysis in breast carcinomas has occasionally revealed cases with a diploid DNA content but with a single hypertetraploid element, the so-called single cell aneuploidy (SCA). To identify the biologic significance of this little known phenomenon, we selected 40 cases with SCA from a series of 599 consecutive operable breast carcinomas. The clinical, pathological and biological characteristics of SCA cases were compared with those of a control group of 40 pure diploid breast carcinomas. Hormonal receptor status, proliferative indexes (Ki-67) and p53 overexpression were determined immunohistochemically and quantitatively evaluated by image analysis. The overexpression of c-erbB-2 was determined semiquantitatively. SCA was observed in 6.6% of cases (40 of 599) and in 17% of otherwise diploid cases (40 of 236). Breast cancers with SCA occur in younger women (mean age 54.75 y vs 61.12 y, P

Summary We describe a case of spontaneous dissecting aneurysm of the circumflex coronary artery in a 44-year-old primigravida at term with no vascular risk factors. Spontaneous coronary artery dissection is a very rare condition with a greater prevalence in women, postpartum in particular. The left anterior descending artery is the most frequently affected. Histologically, the most common finding is a hematoma occupying the outer third of the media, resulting in complete compression of the true lumen. Arterial wall changes during pregnancy together with hemodynamic factors, a lytic action of protease released from eosinophils, and intimal tears are the main hypotheses considered to explain the etiology of spontaneous coronary artery dissection.

Background HER2 overexpression/amplification has been reported to be a predictor of prognosis in breast cancer and a potential marker for selecting the optimal adjuvant chemotherapy. Patients and Methods HER2 expression and its interaction with treatment were retrospectively evaluated in 266 of 348 patients in a trial comparing adjuvant CMF (cyclophosphamide/methotrexate/5-fluorouracil) with weekly epirubicin in stage I/II breast cancer. HER2 expression was determined by immunohistochemistry (IHC) using the monoclonal antibody CB11. Initially, any cell showing definite membrane staining was counted, and HER2 overexpression was analyzed as a continuous variable and as a dichotomous variable, with a cutoff of > 50% of positively stained cells. Subsequently, the same slides were reanalyzed with the HercepTest®. Results Of the 266 tumors immunostained for HER2, 34% exhibited nearly homogeneous staining with > 50% positive cells. When the HercepTest® was applied, 8% of tumors were IHC 3+ and 8% were IHC 2+. At 8 years, no statistically significant difference in relapse-free survival (RFS) and overall survival (OS) was observed between the treatment arms in patients with low versus high HER2 overexpression, although the number of events is low. The OS was statistically shorter in patients with high HER2 overexpression in the CMF arm, whereas no difference was observed in the epirubicin arm, suggesting that patients whose cancer overexpresses HER2 could benefit more from anthracycline-based therapy. Conclusion HER2 overexpression was associated with a poorer OS but not a poorer RFS. However, a Cox regression model did not confirm the prognostic role of HER2 for OS.

The search for single independent prognostic factors in breast cancer has often produced conflicting results. Therefore, prognostic indexes have been compiled by combining several parameters. In this study we compare the Nottingham Prognostic Index (NPI), which is based on traditional prognostic factors (diameter of the neoplasm, lymph node status and histological grade) with the Adelaide Prognostic Index (API), which is based on the tumour diameter and two biological parameters: oestrogen receptors and cell kinetics. We considered 82 cases of breast cancer observed over the period 1987-1990 with a minimum follow-up of 60 months. The NPI gives a better definition of the prognostic profile for each patient. Our results indicate three prognostic groups (good, moderate, unfavourable), which differ with respect to disease-free survival (DFS; P=0.0024) and overall survival (OS; P=0.0033). In contrast, the API scores showed no significant correlation with OS or DFS. The use of prognostic indexes, especially when compiled using traditional parameters, is a useful aid to the clinician, since they can provide a reliable indication of how individual tumours will evolve.

The aim of this study was to evaluate the impact of Bcl-2, retinoblastoma (Rb) and p53 proteins on overall survival of 102 patients with locally advanced and metastatic NSCLC who underwent cisplatin-based chemotherapy.Paraffin-embedded bronchial biopsy and fine-needle biopsy specimens were evaluated by an immunostaining method.Median age of analyzed patients was 61 years. Male/female ratio was 88/14. There were 10 (10%) patients with stage IIIA, 37 (36%) with stage IIIB and 55 (54%) with stage IV NSCLC. Only 15 (15%) tumor specimens had no detectable alterations for analyzed factors. Forty-six samples (45%) had positive immunostaining for p53, 61 (60%) had negative immunostaining for Rb and 8 (8%) had positive immunostaining for Bcl-2. Median and 5-year survival of analyzed population was 12 months and 6%, respectively. In univariate analysis Bcl-2 overexpression, stage (III versus IV) and normal lactate dehydrogenase (LDH) serum levels were associated with better overall survival (P0.02, 0.001 and 0.03). In multivariate analysis, only stage was identified as an independent predictive factor.High frequency of Rb and Bcl-2 loss was detected in patients with advanced NSCLC. P53, Rb and Bcl-2 have not been shown to be independent predictors of survival even if Bcl-2 might have a particular relevance in patients with advanced NSCLC and should be better explored in this setting.

In this study, we retrospectively evaluated the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in 228 and 213 specimens, respectively, from stages I and II breast cancer patients (pts) enrolled in a randomized phase III adjuvant chemotherapy trial comparing epirubicin to CMF, while tamoxifen was given to all postmenopausal pts. The expression of VEGF and MVD was assessed on tissue sections formalin-fixed and paraffin-embedded by immunohistochemical staining using anti-VEGF antibody of human origin and anti-CD34 monoclonal antibody. Univariate and multivariate analysis were performed using chi squared test, log-rank test and Cox's regression model. Sixty four of 228 pts were classified as VEGF positive (28%) with no significant difference in the two treatment arms. In 213 pts evaluated for CD34, 103 pts (48%) were classified as MVD high. No significant association between VEGF and MVD was found, and neither were they correlated with many known prognostic factors such as age, tumor size, nodal status, and histological grade. The only significant correlations observed were between VEGF and estrogen receptor (ER) status (p = 0.013) and between MVD and HER2 overexpression (p = 0.023). At a median follow up of 96 months VEGF and MVD were not correlated with relapse-free survival (RFS) and overall survival (OS) in all pts and in pts assigned to one of the two treatment arms. In conclusion, VEGF and MVD retrospectively evaluated, cannot be considered prognostic factors in node negative (N−) high risk and node positive (N+) breast cancer pts treated with two different regimens of adjuvant chemotherapy.

Background and Objectives: The different and unpredictable outcomes in early-stage non-small cell lung cancer patients requires urgent research concerning the biological pathway of this neoplasm. Our study investigated the frequency of expression and the clinicopathologic and prognostic significance of a series of biological markers in stage I and II resected non-small cell lung cancer. Methods: A total of 99 cases of pathologic stage I and II were analyzed. The mean follow-up of surviving patients was 41 months. The expressions of the following biological markers were tested: bcl-2, p53, Ki-67, angiogenesis, and tumor vessel invasion. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical variables and biological markers using Cox's model for multivariate analysis. Results: Tumoral vessel invasion was present in 22 (22%) pathologic samples, the angiogenesis mean value was 37 ± 13, and median was 35; 13 (13%) patients showed positive immunostaining for bcl-2 oncoprotein. P53 oncoprotein expression was present in 48 patients (48.5%). All samples presented Ki-67 expression (mean value = 25.3 ± 19.3, median = 20). The pathologic staging of the tumor was the most important independent prognostic factor for survival (P = 0.037) and for recurrence of disease (P = 0.040). Tumoral vessel invasion was the only marker with an independent predictive factor for survival and recurrence of disease in the group of patients without lymph node involvement (P = 0.02). Conclusion: Our data do not support a relevant prognostic role for p53, bcl-2, or Ki-67 immunohistochemical markers in non-small cell cancer. Tumor vessel invasion was an independent predictive factor of poor outcome in the group of patients without lymph node involvement. Pathological stage was confirmed as the most important independent prognostic factor.

Prognosis for locoregionally advanced NSCLC patients is poor. Five year survival rates of less than 10 % are reported for patients with mediastinal lymph-node involvement [1]. Efforts to improve this poor prognosis have recently focused on multiple therapeutic modalities including neo-adjuvant chemotherapy [2–6] and give the best reproducible response rates. Since 1988 a phase II trial of this neo-adjuvant chemotherapy combination has been used in patients with clinically apparent N2 to assess response rate, complete resection by surgery and the feasibility of combined treatment.

Male and female noninbred Sprague-Dawley rats 30-36 days of age were given single iv injections of 10 or 5 mg adriamycin (Ad)/kg or 10 mg daunomycin (DM)/kg. Multiple mammary tumors (MT), mostly adenocarcinomas, were observed in 29 and 67% of the females given 10 and 5 mg Ad/kg, respectively, and in 64% of those given 10 mg DM/kg. The mean induction time for females receiving 10 mg Ad/kg was 135 days, for those receiving 5 mg/kg it was 114 days, and for those receiving DM it was only 80 days. Single MT, also mostly adenocarcinomas, were observed an average of 279 days from injection in 31% of the males given 5 mg Ad/kg and an average of 91 days from injection in 37% of the males given 10 mg DM/kg. No tumors were observed in the males given 10 mg Ad/kg, but these survived for only 79 days after treatment.

Aims and Background Amplification/overexpression of HER-2/neu and inactivation of p53 may be reliable parameters for the prognostic assessment of breast carcinomas. Several studies have addressed the prognostic significance of simultaneous expression of these gene abnormalities with controversial results. Methods In this study we analyzed the biopathological profile of 45 breast cancers with both HER-2/neu and p53 overexpression and compared their features with those of 45 randomly selected cases negative for these gene products. Results Tumors with HER-2/neu and p53 coexpression were found in younger patients, were more often multifocal and/or multicentric, were poorly differentiated in 55% of cases and lymph node-positive in 57%, showing a statistically significant difference compared to tumors with neither alteration (11% and 28%, respectively). Moreover, they were prevalently negative for estrogen (71% vs 22%) and progesterone receptors (78% vs 40%) and showed a higher proliferative activity. Conclusions Our data demonstrate that the coexpression of p53 and HER-2/neu is an additive effect in terms of genetic instability reflected by both morphological and biological adverse features; patients with such coexpression should be assigned to specific therapeutic and follow-up protocols.