Genomic instability in chronic viral hepatitis and hepatocellular carcinoma.

Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (HCC). Progressive accumulation of mutations and genomic instability in chronic viral hepatitis might flag an increased risk of HCC development. Genomic instability at dinucleotide microsatellite loci in chromosomes 2, 13, and 17 and at 2 mononucleotide repeat loci was examined in liver tissues from 41 patients, including 30 without HCC (18 patients with chronic hepatitis and 12 with cirrhosis) and 11 with HCC. Genomic instability was detected in 51% of the 41 cases. Allelic imbalance at informative dinucleotide loci occurred in 37% of the cases. In 14 cases (34%), allelic imbalance was detected in chronic hepatitis or cirrhosis without HCC. Allelic imbalance at the chromosome 13 locus was detected in 50% of the cases of chronic hepatitis C. Allelic imbalance at the TP53 chromosome locus and/or at the chromosome 13 locus was significantly more frequent than alterations at the chromosome 2 locus (P =.026). Low-level microsatellite instability was found in 20% of all cases examined and high-level microsatellite instability in 3 patients (7.5%), including 2 cases of chronic hepatitis and 1 case of cirrhosis. Our results show that allelic imbalance occurs frequently in hepatitis-related HCC as well as in chronic hepatitis in patients without HCC. Allelic imbalance at the D13S170 chromosome 13 locus (13q31.2) occurs frequently in chronic hepatitis, suggesting that genomic alterations affecting the long arm of chromosome 13 might be used to monitor the natural progression of chronic hepatitis-associated liver carcinogenesis.

Expression of the ALK protein by anaplastic large-cell lymphomas correlates with high proliferative activity.

A variable fraction of anaplastic large-cell lymphomas (ALCLs) exhibits a t(2;5)(p23;q35) translocation that results in expression of the chimeric hyperphosphorylated protein NPM-ALK (p80). Tumor cells expressing NPM-ALK exhibit markedly enhanced proliferative activity, but comparative cellular kinetic studies on ALK(+) (ALK lymphomas) and ALK(-) lymphomas are lacking. The present study showed that ALK(+) lymphomas, detected with the monoclonal antibody ALKc (n = 17), had significantly higher average values for the proliferation-associated parameters mitotic index, ana/telophase index, growth index (x x mitotic index - apoptotic index, assuming x = 3), percentages of Ki-67(+) cells and fraction of cells expressing cyclin A or B or the cell cycle-regulatory protein p34(cdc2) than did ALK(-) ALCLs (n = 15). Whether this intense proliferative activity contributes to the good response to chemotherapy and favorable outcome of ALK(+) ALCLs remains to be assessed in a larger series of patients. Our findings support the notion that ALK(+) and ALK(-) ALCLs are 2 distinct disease entities.

Congenital mesoblastic nephroma (CMN) with an unusual immunohistochemical feature.

OBJECTIVES: To describe a case of congenital mesoblastic nephroma (CMN) treated by radical nephrectomy with no evidence of relapses after five years in spite of an unusual positivity for proliferating cellular nuclear antigen (PCNA). METHODS: A three-month-old child presented a right renal mass with compression of the inferior vena cava. Excretory urography showed an intrarenal mass with distortion of the calyceal system. There was no evidence of metastasis. Radical nephrectomy was carried out; no adjuvant therapy was given. Histological and immunohistochemical studies were performed. RESULTS: The tumor was a 6 x 6 x 5 cm solitary mass extending into perirenal tissue, involving the hilar vessels but not the ureter. Histologically, it has been classified as a congenital mesoblastic nephroma of the classic variant. Positive reaction for vimentin and actin was observed. Strong positivity for PCNA and negativity for P53 were revealed. CONCLUSIONS: PCNA is considered to be a reliable marker of potential malignancy. This, however, contrasts with the biological behavior of our case. Further evaluation is required for correct interpretation of this additional information and to avoid inappropriate aggressive therapy.