Immunohistochemical study of apoptosis-related Bcl-2 protein and its correlation with proliferation indices (Ki67, PCNA), tumor suppressor genes (p53, pRb), the oncogene c-erbB-2, sex steroid hormone receptors and other clinicopathological features, in normal, hyperplastic and neoplastic endometrium.

The bcl-2 gene codes for a protein which functions to inhibit apoptotic cell death, that involves an intrinsic normal cell death program. Bcl-2 overexpression was originally described in a follicular lymphoma, but more recently bcl-2 expression has been observed in a variety of other human neoplasms. Variation in the frequency of apoptosis in hormone-sensitive tissues, such as the endometrium, is known to occur as a result of hormonal changes in both physiological and pathological circumstances. In this study we examined bcl-2 protein expression in a total of 170 samples of endometrial tissues (18 proliferative endometrium, 14 secretory endometrium, 35 adenomatous hyperplasia and 103 carcinomas). The results were compared with p53, pRb and c-erbB-2 proteins expression, estrogen and progesterone receptors status, with the proliferative activity and with clinicopathological features. The expression of bcl-2 protein was lower in the group of carcinomas, when compared with the cases of adenomatous hyperplasia (p < 0.0001), normal proliferative (p < 0.0001) and secretory endometrium (p = 0.07). In normal proliferative endometrium bcl-2 expression was correlated with PCNA (p = 0.026) and in secretory endometrium it was correlated with ER status (p = 0.042). In hyperplasias, bcl-2 was correlated with PCNA (p = 0.019) and the PR (p = 0.007) expression. In carcinomas, decreased bcl-2 expression was associated with increased tumor grade (p = 0.04). A positive relationship between bcl-2 expression and pRb, as well as PCNA score (p = 0.014 and p = 0.001, respectively), was also found. These results indicate that bcl-2 expression may play a role in the inhibition of apoptosis in endometrial carcinoma and its expression seems to be associated with tumor differentiation and cell proliferation.

Prognostic significance of the deleted in colorectal cancer gene protein expression in high-risk resected gastric carcinoma.

The deleted in colorectal cancer (DCC) gene is a candidate tumor suppressor gene that may be associated with differentiation and proliferation of normal cells. Loss of heterozygosity (LOH) of 18q, where the gene is located, and absence of DCC protein expression have been associated with worse prognosis in certain subgroups of patients with colorectal adenocarcinoma. We studied the prognostic significance of loss-of-protein expression in 66 patients with resected gastric cancer with a high probability of relapse (T3, T4, N+). The DCC protein was detected with immunohistochemistry using an anti-DCC monoclonal antibody on paraffin-embedded sections. The DCC protein expression was present in 51 cases (77.3%) and absent in 15 cases (22.7%). Poorly differentiated and signet ring carcinomas had significantly lower expression than more differentiated tumors (p < 0.05) as did diffuse-type tumors compared to intestinal and mixed (p < 0.01). There was no correlation with proliferation rate, estimated immunohistochemically using an anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody. Absence of DCC protein was an independent favorable prognostic factor (median survival 57 months vs. 18 months, p = 0.0176). The DCC protein expression was correlated with relapse site: all patients with distant metastases were positive for DCC staining, while one-third of patients with local/peritoneal relapse were negative (p < 0.01). In conclusion, DCC protein expression seems to be a significant prognostic factor in high-risk resected gastric cancer. Our results support previous data associating the DCC gene with differentiation and indicate that this gene may play a role in the metastatic potential of these tumors. These findings need to be confirmed by future larger studies.

Solitary plasmacytoma of the spine in an adolescent: a case report.

Solitary plasmacytoma of bone is a rare disease in patients younger than 30 years, and only a few cases have been reported in children and adolescents. We report the findings of a destructive lesion of the spine due to solitary plasmacytoma in an adolescent patient.

Prognostic significance of p53, bcl-2 and Ki-67 in high risk superficial bladder cancer.

BACKGROUND: Although tumor grade and stage are the most accurate prognostic factors in the evaluation of transitional cell bladder cancer, they cannot always predict the true tumor biological potential since superficial tumors of the same stage and grade may have completely different clinical courses. This study was performed in order to examine whether p53, bcl-2 and Ki-67 have any validity in predicting the course of superficial bladder tumors, with high risk for recurrence or progression, over the traditional prognostic factors that are currently used. Furthermore, we investigated whether any one of these markers maintains its prognostic capability after one course of intravesical instillations of IFN gamma. MATERIALS AND METHODS: The immunohistochemical evaluation of bladder tumor specimens, that were obtained transurethrally for the expression of p53, bcl-2 and Ki-67, was performed in 58 patients. After meticulous selection of cut-off values for the expression of the aforementioned markers, twenty-eight patients were treated only with transurethral resection (TURBT only group) while 30 patients received adjuvantly intravesical instillations of interferon gamma. The times to first recurrence and progression were recorded during the follow-up period which ranged from 3 to 36 months (mean 11.7 months). The prognostic significance of tumor stage, grade, presence of CIS, p53, bcl-2 and Ki-67 in determining the risk for recurrence, was studied with both univariate (log-rank test) and multivariate (Cox regression) methods of analysis, separately for the TURBT only group of patients and for those who received instillations. The same analysis was employed for the risk of progression in the overall number of progressed patients. RESULTS: According to both uni- and multivariate analysis of the prognostic significance for tumor stage (T), grade (G), presence of CIS, p53, Ki-67 and bcl-2 in each group of patients, the Ki-67 index was the only independent prognostic factor for recurrence in patients treated with TURBT only (p = 0.0044 univariate, p = 0.031 multivariate). None of the factors which were studied proved to have prognostic significance for recurrence in the group of patients who received adjuvant intravesical instillation with the immunomodulating agent. Although in the univariate analysis all the studied parameters except tumor stage seem to be associated in a statistically significant manner with higher risk for progression, the multivariate analysis did not yield any independent significant prognosticator. The same evaluation was performed only for the patients with grade 2 disease (28) and yielded statistically significantly higher risk for recurrence, both in uni- (p = 0.0081) and in multivariate analysis (p = 0.044) only in the patients with overexpression of Ki-67 who were treated with TURBT alone. CONCLUSION: The Ki-67 proliferative index has an independent validity in predicting those patients with high risk superficial bladder tumors who may recur in a short follow-up period. A similar relationship of Ki-67 overexpression to progression was not detected. The expression of p53 and bcl-2 does not seem to offer any prognostic information in predicting either recurrence or progression over the prognostic factors that are currently used in clinical practice.