Lung resistance-related protein (LRP) expression in malignant ascitic cells as a prognostic marker for advanced ovarian serous carcinoma.

PURPOSE: Ovarian serous carcinoma is an aggressive cancer that often presents with metastatic disease. Although primary tumor and established metastatic foci in the omentum are generally compared to identify proteins involved in drug resistance, we investigated a potential bridge, the malignant cells from ascites, as facilitator of drug resistance and recurrence. METHODS: We evaluated the expression of drug resistance markers P-glycoprotein (P-gp), canalicular multispecific organic anion transporter (MRP2), and lung resistance-related protein (LRP) in malignant cells from ascites and matched omental metastasis from 25 patients with advanced-stage ovarian serous carcinoma who were chemotherapeutic naïve and undergoing initial cytoreductive surgery. Cell viability in vitro, patient response to chemotherapy, and patient survival were correlated with these biomarkers. RESULTS: Of the 25 patients evaluated for a correlation of LRP to 1-year recurrence, we correctly predicted the 1-year recurrence of 24 patients based solely on the presence of LRP in ascitic tumor cells (p=0.01). P-gp and MRP2 were not expressed in malignant cells of ascites or omental metastases. Malignant cells from ascites had higher expression of LRP and were found to be more resistant to carboplatin treatment than cells from omental metastasis (p=0.00375) by in vitro assay. LRP expression in the malignant cells of ascites correlated with carboplatin resistance (p=0.001) by in vitro assay and recurrence at 1 year (p=0.0125). CONCLUSIONS: LRP expression in malignant cells of ascites is a promising marker to predict response to first-line chemotherapy in patients with advanced ovarian serous carcinoma.

Head and neck mucosal malignant melanoma: clinicopathologic correlation with contemporary review of prognostic indicators.

Unlike their cutaneous counterparts, head and neck mucosal malignant melanomas (HNMM) behave much more aggressively and their prognostic markers have not been fully elucidated. Therefore, the aim of this study was to review the clinicopathologic features of a contemporary series of primary HNMM, retrieved from archival material of 2 large medical centers, and to explore the association, if any, between these variables, the clinical features, and outcomes. The clinicopathologic, radiographic, and follow-up information as well as the dominant histologic pattern, mitotic rate, presence/absence of pigmentation, necrosis, ulceration, vascular invasion, and host-associated lymphocytic response were retrieved and recorded. Twenty cases were identified including 1 melanoma in situ. Eight-five percent of tumors arose in the sinonasal tract and 3 (15%) in the oral cavity. After a median follow-up of 25 months, all patients with invasive melanoma developed recurrence and/or metastasis. Local recurrences occurred in 82% of the patients after a median of 12 months, and distant metastasis occurred in 71% of the patients after a median of 13 months. Of those with adequate follow-up, 82% died with disease, and the remaining 3 had recurrent or metastatic disease. Fourth-seven percent of tumors were pigmented, 89% showed at least focal necrosis, and 93% demonstrated ulceration. Sixth-eight percent showed vascular invasion and 63% had a brisk host lymphocytic response. Mitotic rates ranged from 2 to 60/10 high-power fields. The absence of an invasive component might be associated with a better prognosis but other clinical and pathological features that predict outcome, and/or could influence therapy, remain to be determined in HNMM.

Lack of correlation between microvascular density and pathological features and outcomes in sinonasal and oral mucosal melanomas.

Unlike its cutaneous counterpart, prognostic markers for primary mucosal malignant melanoma have not been well elucidated. It has been recently demonstrated that microvascular density (MVD) in cutaneous malignant melanoma has a significant negative correlation with survival; however, this has not been well-studied in mucosal malignant melanoma of the head and neck. This study explores the potential association between MVD, various histological parameters, and the outcome of a series of sinonasal and oral mucosal melanomas. Nineteen such cases were immunostained with CD31 and the MVD was calculated by using Bioquant Image Analysis Software (R and M Biometrics, Nashville, TN). These cases included 16 sinonasal and 3 oral cavity tumors. The 1, 2, 3, 4 and 5 years overall survival rates were 75, 57, 61, 46 and 46%, respectively. The MVD of the tumors ranged from 25.7 to 732 vessels/mm(2) (mean 142.8 vessels/mm(2); median 84.7 vessels/mm(2)). There was no significant correlation between the MVD and the different clinicopathological features seen within the tumors. There was also no correlation between the MVD and relapse free and overall survival. The results of this study suggest that MVD does not correlate with outcome in mucosal melanoma of the head and neck as seen in cutaneous melanomas. Further larger studies are needed to identify predictive and prognostic markers in such melanomas.