Focal microsatellite mutations in relatives with prostatic adenocarcinoma.

Instability of short tandem repeat sequences, microsatellite instability (MI), has been reported to play an important role in the tumorigenesis of various adenocarcinomas, including prostatic adenocarcinoma. Although prostate cancer is not widely recognized as a heriditary cancer, familial clustering is well known. To investigate the frequency of microsatellite instability in familial prostatic adenocarcinomas we analyzed archival tumor tissue from seven paired first degree relatives with prostatic adenocarcinoma. Twelve dinucleotide, nine trinucleotide, six tetranucleotide repeats and the CAG repeat of the androgen receptor gene were screened for MI. Solitary mutations were observed in four separate cases (28.6%) and widespread somatic alterations were not identified. No statistical correlation to pathological characteristics was determined. Our data indicate that microsatellite instability is an uncommon phenomenon in prostatic adenocarcinoma within first degree relatives. Those changes present appear to manifest as focal mutations in contrast to the more global changes seen in MI.

Use of proliferative markers Ki-67 (MIB-1) and proliferating cell nuclear antigen (PC10) in transitional cell carcinoma of the renal pelvis.

Segmental renal resection and improved endourological techniques have resulted in conservative treatment options for transitional cell carcinoma of the renal pelvis. These techniques have increased the need for more objective measures of biological behavior. We applied two immunohistochemical markers of cellular proliferation, proliferating cell nuclear antigen (PCNA; PC10) and Ki-67 (MIB-1), to 58 archival cases of renal pelvic transitional cell carcinomas and correlated the percentage of positive cells to grade, stage, and survival, and to one another; mitotic counts (mitoses/10 high-power fields) were also performed. Expression of PCNA showed a significant difference between grades 1, 2, and 3 tumors (P = 0.05) and between superficial (Ta, T1) and invasive tumors (T2-4) (P = 0.02). There was a significant overlap, however, in the percentage of cells staining between the grades as well as the stages. PCNA staining did not correlate with survival and did not identify a subset of patients with low-stage, low-grade tumors with a poorer prognosis. The Ki-67 score exhibited a stronger correlation with grade (P = 0.001), and there was a trend of increasing Ki-67 expression with higher stage tumors, but this did not reach statistical significance (P = 0.10). Ki-67 showed comparable findings to PCNA with regard to survival and overlap in staining between the grades and stages. Mitotic counts did correlate with grade (P = 0.003) but not stage or survival. This study demonstrates that cellular proliferation, as determined by the immunohistochemical markers, Ki-67 and PCNA, is related to grade and, to a lesser extent, stage, but the use of these markers as measures of biological behavior in clinical practice may be limited.

Histopathological features and p53 nuclear protein staining as predictors of survival and tumor recurrence in patients with transitional cell carcinoma of the renal pelvis.

PURPOSE: We determine which histopathological features are predictive of recurrence and cause-specific survival in renal pelvic transitional cell carcinoma. MATERIALS AND METHODS: Univariant and multivariant analysis was done on material from 67 patients. RESULTS: Univariate and multivariate analysis identified lamina propria invasion, grade 3 tumors and capillary-lymphatic invasion as predictors of disease-specific survival. Multicentric disease was the sole independent predictor of recurrence. Multicentric disease and lamina propria invasion were independent predictors of recurrence-free survival. Also, p53 over-expression was not statistically associated with any of the studied prognostic factors. CONCLUSIONS: Histopathological features remain the cornerstone of prognostic assessment for renal pelvic transitional cell carcinoma.

Hip and knee replacement as a relative contraindication to laparoscopic pelvic lymph node dissection.

PURPOSE: We investigated the effect of lower extremity joint prostheses on subsequent laparoscopic pelvic lymph node dissection. MATERIALS AND METHODS: We reviewed the records and pathology studies of 5 patients who underwent laparoscopic pelvic lymph node dissection subsequent to total hip or knee replacement from 1990 through 1995. RESULTS: Four of the 5 laparoscopic operations were complicated, 3 were unsuccessful in obtaining bilateral pelvic lymph nodes and 2 required conversion to an open procedure. Examination of the lymph nodes revealed sinus histiocytosis in the 4 cases in which nodal tissue was removed. CONCLUSIONS: The increased risk of complications in certain patients with lower extremity joint prostheses may contraindicate attempted laparoscopic pelvic lymph node dissection.

Microsatellite instability in adenocarcinoma of the prostate.

Instability of dinucleotide tandem repeat sequences has been reported to play a major role in the carcinogenic pathway of familial colon cancer, as well as a potential role in the carcinogenesis of other sporadic neoplasms. To determine the frequency of short tandem repeat instability in adenocarcinoma of the prostate, we studied 40 tumors that were stratified according to tumor grade. The tissue samples were screened with di-, tri- and tetranucleotide markers spanning a wide range of chromosomal loci, including an androgen receptor gene trinucleotide repeat. Microsatellite instability was observed overall in only one of the 40 (2.5%) prostate adenocarcinomas studied. This replication error-positive tumor demonstrated repeat length alterations at two loci. Five other tumors showed an alteration in microsatellite size at a single locus. These tumors were not considered to have the microsatellite instability phenotype. All changes were identified either within tetranucleotide sequences or within the androgen receptor gene repeat (4 or 20 total markers analyzed). Both repeat length expansions and contractions were identified. The replication error-positive case also included separate metastatic nodal tissue. Additional microsatellite analysis of the metastatic tumor tissue revealed allelic patterns identical with the normal tissue control. Our data indicate that microsatellite instability is rare in prostate adenocarcinoma. Therefore, observation of this low replication error frequency suggests that most prostate carcinomas develop in the absence of widespread accumulation of somatic mutations in short tandem repeat sequences. Additionally, these genetic alterations appear to occur more often in tetranucleotide repeat sequences as well as in an androgen receptor gene trinucleotide repeat.