Reelin expression in human prostate cancer: a marker of tumor aggressiveness based on correlation with grade.

Reelin is a glycoprotein that plays a critical role in the regulation of neuronal migration during brain development and, since reelin has a role in the control of cell migration, it might represents an important factor in cancer pathology. In this study, 66 surgical specimens of prostate cancer were analyzed for reelin expression by immunohistochemical method. The reelin expression was correlated with Gleason score and individual Gleason patterns. Reelin expression was found in 39% prostate cancers. Stromal tissues, normal epithelial cells and prostate intraepithelial neoplasia (PIN) of any grade around and distant from cancer were always negative for reelin. Reelin was found in malignant prostatic epithelial glands of 50% cases Gleason score 10, 52% Gleason score 9, 56% Gleason score 8, 18% Gleason score 7, while no sample of prostate cancers with Gleason score 6 showed reelin expression (P=0,005). As reelin staining is frequently found in high Gleason score prostate cancers, we explored whether reelin expression is influenced by single Gleason patterns. While Gleason 3 pattern did not show reelin immunoreactivity, reelin expression was found in 35% Gleason 4 patterns and 45% Gleason 5 patterns (P<0.001). Our results demonstrated for the first time that reelin is expressed in prostate cancer and not in benign prostate tissue and its expression occurs in higher Gleason score and correlates significantly with increasing of single Gleason patterns. This suggests reelin may behave as a specific histological marker and may represent a useful biomarker to predict aggressive phenotypic behavior of prostatic cancer cells.

COX-2 expression of ampullary carcinoma: correlation with different histotypes and clinicopathological parameters.

Epidemiological studies suggest that regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced incidence of gastrointestinal cancer. Several lines of evidence indicate that the antineoplastic effect of NSAIDs is attributable to COX-2 inhibition. The aim of our study was to assess COX-2 expression in a series of primary untreated ampullary carcinomas and its possible correlation with clinicopathological parameters. In the present study, 45 surgical specimens of invasive ampullary carcinomas were histologically classified into pancreaticobiliary, intestinal, and unusual types. COX-2 expression by immunohistochemical method was analyzed. High COX-2 expression was detected in 35 (77.8%) ampullary carcinomas. Among these, 20/21 (95.2%) were classified as intestinal, 9/18 (50%) pancreaticobiliary, and 6/6 (100%) unusual type. A significant statistical difference in terms of COX-2 expression was found between pancreaticobiliary vs intestinal type (P=0.002). Furthermore, a negative significant statistical correlation was found between T factor and COX-2 expression (P=0.047). The different COX-2 expression among histopathological types supports the concept of histogenetical difference of ampullary carcinomas. Furthermore, the high rate of COX-2 expression in the intestinal subtype of ampullary carcinoma may represent the rational for a histotype-tailored therapy targeting COX-2.

Thymidylate synthase expression in normal colonic mucosa: a predictive marker of toxicity in colorectal cancer patients receiving 5-fluorouracil-based adjuvant chemotherapy.

OBJECTIVES: We retrospectively evaluated the relevance of thymidylate synthase (TS) expression in normal colonic mucosa as a predictive factor of toxicity in colorectal cancer patients receiving adjuvant fluorouracil (5-FU)-based chemotherapy. METHODS: TS expression was immunohistochemically assessed on normal colonic mucosa from 50 patients with colorectal cancer Dukes' stages B (15 patients) and C (35 patients) treated with 5-FU-based adjuvant chemotherapy. RESULTS: The incidence of grade 2-3 diarrhea and stomatitis (according to WHO) was demonstrated to be significantly higher in patients with low nuclear TS expression in normal mucosa than in those with high TS expression (p < 0.0001). Moreover, patients with low TS expression in normal colonic mucosa developed weight loss and worsening of the performance status (according to ECOG score) more commonly than patients with high TS expression (p = 0.005 and p = 0.02, respectively). Furthermore, low TS expression in normal colonic mucosa significantly correlated with a higher rate of a delay of chemotherapy courses, dose reduction and treatment discontinuation. CONCLUSIONS: Immunohistochemical TS expression in normal colonic mucosa may represent an important predictive parameter for identifying a subset of patients with a high risk of developing severe 5-FU-related toxicities.