ABSTRACT
High rates of early colorectal cancers [CRC] are observed in Tunisia suggesting genetic susceptibility. Nevertheless, up to now no molecular studies have been performed in the Tunisian population. To evaluate the clinical and genetic characteristics of Tunisian families suspected of hereditary nonpolyposis colorectal cancer [HNPCC] and to identify new tumoral markers for CRC susceptibility leading to distinguish patients with sporadic CRC from those with familial CRC, like HNPCC. 31 unrelated families suspected of HNPCC were screened for germline mutations in MMR genes. We have also analyzed tumoral phenotype and the genetic characteristics of tumors from 51 patients with CRC meeting the Bethesda criteria. 10 different germ line mutations, 8 of which were novel, were identified in 11 out of the 31 families [35.5%], 5 in MSH2 and 5 in MLH1. Our results showed that MUC5AC expression was more frequent in patients with family history of CRC [p=0.039]. The analysis of MUC5AC expression might be very beneficial in the detection of Tunisian patients with high susceptibility to CRC
ABSTRACT
Carcinoma of unknown primary [CUP] origin is defined as histologically confirmed metastatic carcinoma in the absence of a detectable primary site at the time of making therapeutic decision. To report epidemiological, clinical, histopathological, therapeutic, and prognostic features of CUP's patients collected at the Salah Azaiez institute [SAI]. We reviewed retrospectively the files of 437 CUP-patients in SAI between January 1994 and December 2006. We analyzed their epidemiological, clinical, histological and therapeutic features and classify patients in favourable and unfavourable subsets. Statistical analysis was performed with R software. Survival curves were made with the method of Kaplan-Meier. We collected 437 patients with a median age of 60 years and a sex-ratio of 1.8. CUP are metastatic to lymph nodes [56.5%], bones [29.7%] and liver [28%]. 33% of patients had a unique site of metastases. Adenocarcinoma represented 50.5% of cases while 10.5% are classified in the favourable subgroup. 141 out 437 patients received palliative chemotherapy, 83% of them by cisplatin-based regimens obtaining 13% [58 patients] of objective response. Median survival was 7 months. 24 out 58 patients [41%] relapsed. Poor prognostic factors for survival were: multiple metastases [p=0.00033], >3 sites [p=0.03], undifferentiated carcinoma and adenocarcinoma [p>0.0001], liver metastases [p=0.0137], bone [p=0.00653] and adrenal gland [p=0.0334] metastatic sites. Patients who underwent chemotherapy [p>0.001] and who received cisplatbased regimen had better survival [p=0.01]. Our retrospective study done in the context of a minimal and biological work-up confirmed the difficulty to find the primary in CUP