Carcinoid tumors are neuroendocrine neoplasms that are encountered either sporadically or as part of a familial syndrome, most notably-multiple endocrine neoplasia type 1 (MEN1). The MEN1 gene localizes to chromosome 11 (11q13) and presumably functions as a tumor suppressor gene. The molecular mechanisms underlying carcinoid tumor development and their clonal composition remain largely unknown. To establish whether carcinoid tumors develop via a mechanism similar to other MEN1-associated tumors, and indirectly determine their clonal composition, we analyzed 36 sporadically occurring carcinoid tumors with 16 chromosome 11 microsatellite markers, mostly from around the MEN1 region for loss of heterozygosity (LOH). Twenty one tumors (58%) displayed LOH of at least three markers, five lost almost an entire allele and the rest displayed a discontinuous pattern. Similar, but less extensive analysis was also carried out for 10 additional carcinoid tumors from Brazil, 6 of the 10 showed LOH with at least one marker. Overall, 36 of 46 tumors (78%) displayed LOH. In addition, 20 of 46 (43%) tumors exhibited a pattern of genomic instability. Thus, the majority of sporadically occurring carcinoid tumors are monoclonal whose tumorigenesis involves inactivation of a tumor suppressor gene on chromosome 11 and DNA mismatch repair genes mutations.
Background. The course of patients with renal cell carcinoma may be considerably different. Approximately 50% with presumed localized disease have metastases after nephrectomy. Pathologic stage at diagnosis, histologic grade, and histologic type have been considered the most important predictors of prognosis. Nevertheless, subsets of patients within a specified stage and grade may have considerable differences in disease progression and survival.
Methods. Flow cytometric nuclear DNA analysis was used to study pathologic Stage I or II renal cell carcinoma in 54 patients who underwent radical nephrectomy between 1974 and 1983.
Results. Sixty‐three percent of the tumors were diploid, and 37% aneuploid. A DNA diploid pattern was more common among Stage I tumors than Stage II tumors (69% versus 33%; P < 0.04). Progression occurred in 31% of the diploid tumors, whereas among the aneuploid group the progression rate reached 59% (P < 0.06). Considered as a single indicator, DNA ploidy pattern was strongly associated with patient survival. Ten years after surgery 79% of the patients who had diploid tumors and 50% of those with aneuploid tumors were alive (P < 0.02).
Conclusions. Nuclear DNA ploidy may serve as an important prognostic variable for patients with early stage renal cell carcinoma.
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