Background: The Paris System (TPS) acknowledges the need for more standardized terminology for reporting urine cytopathology results and minimizing the use of equivocal terms. We apply TPS diagnostic terminologies to assess interobserver agreement, compare TPS with the traditional method (TM) of reporting urine cytopathology, and evaluate the rate and positive predictive value (PPV) of each TPS diagnostic category. A survey is conducted at the end of the study. Materials and Methods: One hundred urine samples were reviewed independently by six cytopathologists. The diagnosis was rendered according to TPS categories: negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells (AUC), low-grade urothelial neoplasm (LGUN), suspicious for high-grade urothelial carcinoma (SHGUC), and high-grade urothelial carcinoma (HGUC). The agreement was assessed using kappa. Disagreements were classified as high and low impacts. Statistical analysis was performed. Results: Perfect consensus agreement was 31%, with an overall kappa of 0.362. Kappa by diagnostic category was 0.483, 0.178, 0.258, and 0.520 for NHGUC, AUC, SHGUC, and HGUC, respectively. Both TM and TPS showed 100% specificity and PPV. TPS showed 43% sensitivity (38% by TM) and 70% accuracy (66% by TM). Disagreements with high clinical impact were 27%. Of the 100 cases, 52 were concurrent biopsy-proven HGUC. The detection rate of biopsy-proven HGUC was 43% by TPS (57% by TM). The rate of NHGUC was 54% by TPS versus 26% by TM. AUC rate was 23% by TPS (44% by TM). The PPV of the AUC category by TPS was 61% versus 43% by TM. The survey showed 33% overall satisfaction. Conclusions: TPS shows adequate precision for NHGUC and HGUC, with low interobserver agreement for other categories. TPS significantly increased the clinical significance of AUC category. Refinement and widespread application of TPS diagnostic criteria may further improve interobserver agreement and the detection rate of HGUC.
C-MET proto-oncogene is a tyrosine kinase situated on chromosome 7. C-MET and its ligand hepatocyte growth factor/scatter factor (HGF/SF) play a role in proliferation, differentiation and organ development. C-MET genetic aberrations are found associated with driving tumorigenesis. In this retrospective study, we reviewed molecular analysis data gathered from a cancer institute during a two-year period (2010-2012). Upon detection of tumors harboring c-MET mutations, we determined the status of the other mutations tested and evaluated c-MET expression by fluorescent in-situ hybridization (FISH). Our search resulted in identification of 134 c-MET mutations, 44% of which had mutations of at least one of the other genes tested. No c-MET expression aberrancy was detected in this subset by FISH. Survival amongst the patients with surgically resected metastatic colorectal cancers (CRC) was slightly better in those with only a c-MET mutation compared to those with no mutation detected, although the difference was not statistically significant. When c-MET inhibition becomes an integrated part of chemotherapy practice, our observed frequency of co-mutations will be an argument for utilizing c-MET targeted treatment in combination with other targeted drugs and therapeutic strategies. Larger studies can aid to further parse out c-MET prognostic and therapeutic significance.
Primary ovarian serous carcinoma patients presenting with regional lymph node metastasis without extrapelvic peritoneal metastasis are considered International Federation of Gynecology and Obstetrics (FIGO) Stage IIIC. We studied their controversial survival compared with patients with extrapelvic peritoneal metastasis in same Stage IIIC. We included primary peritoneal carcinoma patients with lymph node metastasis to investigate whether primary site of tumor has a prognostic role. Charts of patients treated at the MD Anderson Cancer Center in Houston, TX; from 1992 to 2010 were reviewed. Primary ovarian serous carcinoma patients were grouped into patients with lymph node metastasis without extrapelvic involvement (Group 1, n=13) and patients with additional extrapelvic peritoneal involvement (Group 2, n=43). Group 3 patients (n=38) were selected using similar criteria as Group 2 but with negative lymph nodes. Group 4 patients were those with primary peritoneal serous carcinoma with lymph node metastasis (n=13). Group 1 patients had statistically significant better overall survival compared with the rest of the groups. Overall survival was significantly better in Groups 4 versus 2 and Groups 3 versus 2. Primary ovarian serous carcinoma patients with lymph node metastasis without extrapelvic peritoneal involvement have better survival than those with additional extrapelvic peritoneal involvement. Primary peritoneal serous carcinoma patients with lymph node metastasis have better survival than those with primary ovarian serous carcinoma with peritoneal and lymph node metastasis. Ovarian serous carcinoma patients with extrapelvic peritoneal involvement alone have better survival than those with extrapelvic peritoneal involvement and lymph node metastasis. These findings support the proposition to revise the FIGO staging system, especially for Stage IIIC patients, in order to reflect these prognostic differences.
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