Mol Pathol

Imprinted H19 oncofetal RNA is a candidate tumour marker for hepatocellular carcinoma.

Year 1998
Ariel I. Miao HQ. Ji XR. Schneider T. Roll D. de Groot N. Hochberg A. Ayesh S.
Department of Pathology, Hadassah University Hospital Mount Scopus, Jerusalem, Israel. ariel@hadassah.org.il
AIMS/BACKGROUND: To study the expression of the H19 gene in hepatocellular carcinoma. H19 is an imprinted, maternally expressed gene, which is tightly linked, both physically and functionally, to the paternally expressed insulin-like growth factor 2 (IGF II). IGF II is known to be involved in liver carcinogenesis. H19 was first discovered in the fetal mouse liver to be under the same regulatory genes as alpha fetoprotein (alpha FP), a widely used tumour marker for hepatocellular carcinoma. METHODS: Using both radioactive and non-radioactive in situ hybridisation, the expression of the H19 gene was compared with the presence of alpha FP, as demonstrated by immunohistochemistry, in 18 cases of hepatocellular carcinoma. RESULTS: H19 expression was present in 13 of 18 cases, whereas staining for alpha FP was positive in only nine of 18 cases. Concordance was found in 12 of 18 tumours (66.7%). In general, the staining pattern for H19 was more diffuse than the immunohistochemical staining for alpha FP. CONCLUSIONS: The addition of a non-radioactive in situ hybridisation assay for H19 RNA to the panel of tumour markers used for the histopathological and cytological diagnosis of hepatocellular carcinoma might be useful.

Expression of mdm2 and p53 in epithelial neoplasms of the colorectum.

Year 1998
Hao XP. Gunther T. Roessner A. Price AB. Talbot IC.
Academic Department of Pathology, Northwick Park and St Mark's NHS Trust, Harrow, UK.
AIMS: To evaluate the respective roles of mdm2 (murine double minute 2) and p53 in the development of colorectal carcinoma. METHODS: Formalin fixed, paraffin wax embedded tissues from 72 sporadic adenomas and 55 carcinomas were investigated by means of immunohistochemistry for mdm2 and p53. RESULTS: mdm2 was expressed weakly in 17 of 72 (23.6%) adenomas and in 14 of 55 (25.4%) carcinomas. p53 was expressed in 19 of 72 (26.4%) adenomas and in 23 of 55 (41.8%) carcinomas. Four adenomas and five carcinomas showed positive staining for both proteins. Overexpression of p53 in adenomas was associated with moderate and severe dysplasia but not with tumour size. No associations were found between the expression of mdm2 and either the degree of dysplasia or tumour size. In carcinomas, neither the expression of p53 nor mdm2 correlated with Dukes's stage, metastasis, or differentiation. No associations were found between the expression of p53 and mdm2 in either adenomas or carcinomas. CONCLUSIONS: Although mdm2 has been reported to be an oncogene, it does not appear to play a major role in the development of colorectal carcinoma.

Allelic imbalance and microsatellite instability of the DCC gene in colorectal cancer in patients under the age of 35 using fluorescent DNA technology.

Year 1998
Chetty R. Naidoo R. Schneider J.
Department of Pathology, University of Natal, School of Medicine, Durban, South Africa.
AIM: To assess allelic imbalance and microsatellite instability in the region of the "deleted in colorectal cancer" (DCC) gene on chromosome 18q using fluorescent DNA technology in colorectal cancer in patients under the age of 35. METHODS: Thirty two cases of colorectal cancer in patients under the age of 35 and with no family history of colon cancer were retrieved. DNA was extracted by standard methods, polymerase chain reaction (PCR) was performed using Cy5 labelled primers to microsatellite markers (D18S21, D18S34, and D18S58) in the DCC gene. The results were analysed using software attached to an automated DNA sequencer. RESULTS: The patients ranged in age from 17 to 35 years. Nineteen were women, all had left sided tumours (tumours distal to the splenic flexure). Twenty eight cases were either stage C or D (using the Astler Coller system). The informativity of the three markers were as follows: D18S21, 25 of 32 (78.1%); D18S34, 18 of 32 (56.25%); D18S58, 24 of 32 (75%). Allelic imbalance for the markers, after excluding homozygous and microsatellite instability cases, was: D18S21, 31.8%; D18S34, 11.7%; and D18S58, 0%. Nine cases showed allelic imbalance for both D18S21 and D18S34, yielding a combined allelic imbalance frequency of 39.1%. Ten cases showed microsatellite instability in at least one marker, with microsatellite instability seen most commonly for D18S58. Three cases showed microsatellite instability for all three markers. CONCLUSIONS: Approximately 39% of cases showed allelic imbalance for D18S21 and D18S34 markers, while microsatellite instability was found in 31.25% of cases. This figure is higher than that encountered in sporadic colorectal cancer over the age of 50, suggesting a role for the DNA repair genes in the pathogenesis of these cancers occurring under the age of 35.