Non-random trisomies of chromosomes 5, 8 and 12 in the prolactinoma sub-type of pituitary adenomas: conventional cytogenetics and interphase FISH study

Specimens from 53 pituitary adenomas (PAs), including 17 NFPA, 16 PRL-, 9 ACTH-, 9 GH- and 2 TSH-secreting tumors, underwent cytogenetic analysis by the direct and short-term culture methods. Only 8 tumors (15%) appeared to have an abnormal karyotype. To increase the resolution of cytogenetic analysis, direct preparations from 31 PAs were investigated by interphase FISH with probes specific for chromosomes 5, 8, 12 and X, for which gain in pituitary tumors has been reported. Of these 31 PAs, 17 (54.8%) had an abnormal dosage of one or more of the 4 chromosomes tested. Separate or combined trisomies of chromosomes 5, 8 and 12 were found in 10/10 prolactinomas and in 4/9 NFPA, whereas the combined loss of chromosomes 5 and 8 was observed in 1/6 ACTH- and 1/6 GH-secreting PAs. Present and earlier data on 23 PAs showed that tumors with the highest frequency of abnormal karyotypes revealed by cytogenetics and/or interphase FISH were PRL (78%), followed by NFPA (26%) and GH (18%). Recurrent structural rearrangements affecting chromosomes 1, 3 and 12 were also identified in prolactinomas, which therefore appear to be the only pituitary adenoma sub-type with a defined trend of tumor-specific chromosomal changes. Cytogenetic and FISH analyses of different pituitary tumor sub-types indicate that they may harbour genetically distinct lesions.