Chromosomal Gains Demonstrated by Fluorescent In Situ Hybridization Are Helpful in the Diagnosis of Atypical Hepatocellular Neoplasms
S Kakar, JP Grenert, E Pease, O Adeyi, LD Ferrell. UCSF, San Francisco; Univ of Toronto, Toronto, Canada
Background: It can be difficult to distinguish well-differentiated hepatocellular carcinoma (HCC) from hepatic adenoma (HA) based on morphology alone.Gains of chromosomes 1 and 8 are the earliest cytogenetic abnormalities in HCC, and have not been observed in HA.We explored the utility of fluorescent in situ hybridization (FISH) to identify cytogenetic aberrations for the diagnosis of atypical hepatocellular neoplasms occurring in noncirrhotic liver.
Design: FISH analysis using centromeric probes for chromosomes 1,8,X and locus specific probe for c-myc was performed in 35 hepatocellular neoplasms(HA=11, AHN=12, HCC=12). The signals were counted in 100 tumor nuclei per case as well as 200 normal hepatocyte nuclei. The designation of AHN was used in two situations: HA-like morphology in atypical setting (women >50 years and <15 years, and all men) and HA-like morphology with focal atypical areas (small cell change,abnormal trabeculae) that were insufficient for a definite diagnosis of HCC.
Results: None of the HAs showed gains at any of the four chromosomes (0/11). Gains involving at least one locus were seen in 7 (58%) well-differentiated HCCs and 7 (58%) AHNs (see table). Gains of chromosome 1 were seen in all AHNs (100%) and 6 (85%) HCCs. Gains of all loci tested (chromosomes 1,8,X and c-myc) were seen in 3 AHNs and 2 HCCs. One HCC case showed c-myc gains with no other abnormalities. Recurrence and/or metastasis were observed in 3 (25%) AHNs.
Conclusions: Cytogenetic aberrations characteristic of well-differentiated HCC are seen in majority of AHNs (males of any age, females outside the 15-50 year group or with focal atypical morphology). These tumors can recur and metastasize even though they morphologically resemble adenoma. Chromosome 1 gain by FISH was the most common abnormality and was observed in all the abnormal AHN cases. However the sensitivity of the FISH assay using centromeric probes is relatively low as only 58% of histologically diagnosed well-differentiated HCC were cytogenetically abnormal. Examination of additional loci and use of locus specific probes in addition to centromeric probes is likely to increase the sensitivity of diagnosis.
Drs. Kakar and Grenert are equal contributors
|No gains||1+ only||1+ X+||1+,8+,myc+,X+||myc+ only|
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 168, Tuesday Morning