Allelotypes and fluorescence in situ hybridization profiles of poorly differentiated endocrine carcinomas of different sites.
OBJECTIVE
The aim of this work was to investigate the genotypic profiles of 36 poorly differentiated endocrine carcinoma (PDEC) of different sites to verify if their very similar phenotype may reflect similar pattern of genetic anomalies and if useful diagnostic or prognostic markers may be pointed out.


METHODS
All tumors were microallelotyped at 57 microsatellite on 11 autosomes and the allelotypes of a selected panel of tumors were validated by interphasic fluorescence in situ hybridization with centromeric probes for chromosomes 1, 3, 6, 11, 17, and 18 and a probe specific for p53.


RESULTS
Regardless of the primary sites, PDECs exhibit very complex allelotypes (86%) and TP53 allelic imbalance (89%). Among these cases, fluorescence in situ hybridization analysis confirmed the presence of multiple aneusomies and a chromosome instability phenotype. Very low percentage of allelic imbalance (AI) and few aneuploidies were detected in only five PDECs for which an overall longer survival was observed. We found recurrent AI on 3p, 5, and 11q13 in lung PDECs, on 5q21, 8p, and 18q21 in colorectal PDECs and on 7 and 11q22 in gastric PDECs. Significantly better outcome was observed in patients with PDEC exhibiting 8q AIs and absence of AI at chromosome regions 6q25 and 6p.


CONCLUSIONS
The concurrence of p53 inactivation and aneuploidies or chromosome instability are the main features of PDECs. However, the specific allelotypes observed in relation to primary site support the hypothesis that PDECs and exocrine carcinomas of all sites may share early pathogenetic mechanisms. Molecular markers of potential diagnostic and prognostic values for PDECs of different sites have been identified.
Furlan
Daniela
D
Department of Human Morphology, Anatomic Pathology Unit, University of Insubria, Ospedale di Circolo, Viale Borri 57, 21100 Varese, Italy. daniela.furlan@uninsubria.it
Bernasconi
Barbara
B
Uccella
Silvia
S
Cerutti
Roberta
R
Carnevali
Ileana
I
Capella
Carlo
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D043171:Chromosomal Instability / Q000235:genetics*; D004701:Endocrine Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016019:Survival Analysis