• Cutaneous epithelioid angiosarcoma: a clinicopathological study of four cases.

      Prescott, R J; Banerjee, Saumitra S; Eyden, Brian P; Haboubi, N Y; Department of Pathology, Bolton General Hospital, UK. (1994-11)
      Four cases of cutaneous epithelioid angiosarcoma are described together with the potential diagnostic trap of mistaking these tumours for poorly differentiated carcinoma or malignant melanoma. The immunophenotypic profile using four endothelial markers showed positive staining in all cases for factor VIII related antigen in a predominantly paranuclear dot-like fashion and for CD31 (JC70); in three cases for CD34 (QB-END/10) and in two cases with UEA-1. All four cases were cytokeratin (CAM 5.2 and AE1/AE3) negative in contrast to the positive staining reported at non-cutaneous sites. Aberrant S-100 protein expression was seen in one case. In two cases subsequent recurrences showed better differentiation than the original tumour. Electronmicroscopy confirmed the absence of non-endothelial lines of differentiation but failed to reveal Weibel-Palade bodies.
    • An evaluation of five different methods for estimating proliferation in human colorectal adenocarcinomas.

      Wilson, Malcolm S; Anderson, Elizabeth; Bell, J C; Pearson, J M; Haboubi, N Y; James, Roger D; Schofield, Philip F; Department of Clinical Research, Christie Hospital NHS Trust, Manchester, UK. (1994-10)
      Five different methods of determining cell proliferation have been compared in samples taken from a group of 125 human colorectal tumours labelled in vivo with iododeoxy-uridine (IUdR). The labelling index (LI) was obtained immunocytochemically using monoclonal antibodies against proliferating cell nuclear antigen (PCNA), the Ki67 antigen and IUdR (IUdRimm). Incorporation of IUdR was also determined flow cytometrically (IUdRfcm) and PCNA expression was measured in both formalin- and methanol-fixed tissue (PCNAf and PCNAm respectively). There was significant variation in the results obtained both within and between the different assays. Paired analysis of the data showed that the correlation between the different methods of determining the LI was poor. However, the IUdRfcm LI was significantly correlated with both IUdRimm (r = 0.39; n = 78; P < 0.001 by Spearman's test) and Ki67 LIs (r = 0.32; n = 87; P < 0.001). The IUdRimm LI was also significantly related to the Ki67 LI (r = 0.44; n = 60; P < 0.001). The median IUdRfcm and IUdRimm LIs were significantly higher in the aneuploid vs. the diploid tumours (17.4% vs. 6.2% for IUdRfcm; 23.2% vs. 18.9 for the IUdRimm; P < 0.001 and P = 0.014 respectively by Mann-Whitney U-test) but none of the other proliferative indices showed this relationship. Finally, none of the LIs showed a significant association with the clinical characteristics of the tumours such as stage, grade, age, sex or fixity. The findings of this investigation highlight the need for carefully controlled studies when assessing the value of proliferation markers in solid human tumours.
    • K-ras gene mutation in colorectal adenomas and carcinomas from familial adenomatous polyposis patients.

      Boughdady, I S; Kinsella, Anne R; Haboubi, N Y; Schofield, Philip F; Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK. (1992-08)
      Colorectal adenomas and carcinomas from familial adenomatous polyposis (FAP) patients were screened for the presence of K-ras gene mutations at codon 12 using an in vitro amplification step (polymerase chain reaction) followed by dot blot analysis using oligonucleotide probes specific for different mutations at codon 12. We examined 28 colorectal adenomas and two colorectal carcinomas from 12 FAP patients and observed a mutation at codon 12 in seven adenomas and in both carcinomas. The frequency of K-ras gene mutations in colorectal tumours from FAP patients is similar to those in cases of sporadic adenomas and sporadic colorectal carcinomas indicating that the mechanisms involved in their development may be similar.
    • K-ras gene mutations in adenomas and carcinomas of the colon.

      Boughdady, I S; Kinsella, Anne R; Haboubi, N Y; Schofield, Philip F; Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK. (1992-08)
      DNA extracted from 29 colorectal carcinomas and 40 sporadic adenomas was amplified by the polymerase chain reaction (PCR) and analysed for the presence of K-ras gene mutations at codon 12 using a panel of synthetic oligonucleotide probes specific for normal and mutated sequences. The presence of mutations was correlated with various histopathological and clinical data. Ten carcinomas (34.5%) and 14 sporadic adenomas (35%) showed K-ras mutations at codon 12. In the carcinoma group, no apparent correlation was found between the presence of mutant oncogenes and the degree of histological differentiation, Dukes' staging or the development of distant metastasis. In the adenoma group, the frequency of mutations increased with the size of the adenoma and the severity of the dysplastic changes. This study confirms that ras gene mutations are common and early events in colon carcinogenesis. They appear to give a selective growth advantage to those polyps with mutations which leads to their increase in size and thus possibly prepare the ground for malignant transformation.
    • Promutagenic methylation damage in bladder DNA from patients with bladder cancer associated with schistosomiasis and from normal individuals.

      Badawi, Alaa F; Mostafa, M H; Aboul-Azm, T; Haboubi, N Y; O'Connor, Peter J; Cooper, Donald P; Institute for Graduate Studies and Research, University of Alexandria, Egypt. (1992-05)
      Radioimmunoassays (RIAs) have been used to detect the promutagenic lesion O6-methyldeoxyguanosine (O6-MedG) in DNA isolated from the bladder tissues of Egyptian patients presenting with bladder carcinoma and concomitant schistosomiasis (bilharziasis), a parasitic disease known to be associated with the presence of N-nitrosamines in the urine. Alkylation damage was present in the DNA of the majority of the samples (44/46, 96%); 38 samples were of tumour tissue and 8 from uninvolved bladder mucosa. Levels of O6-MedG ranged from undetectable (ND; i.e. less than 0.01 mumol O6-MedG/mol dG) to 0.485 mumol/mol dG with an overall mean of 0.134 +/- 0.10 mumol/mol dG, including the two samples that were below the limit of detection. In contrast, methylation damage was detected in only 4/12 (33%) of the DNA samples from normal bladder tissue of European origin. In these samples levels of O6-MedG ranged from ND to 0.225 mumol/mol dG with an overall mean of 0.046 +/- 0.082 mumol O6-MedG/mol dG. These results confirm that alkylation events can be detected in the DNA of schistosome-infected human bladder tissue. The methylation of uninvolved and tumour tissue DNA to similar extents suggests that the alkylating intermediate may have been present in the urine. These results indicate the need for further investigation to determine whether relationships exist between levels of DNA damage and the prevalence of schistosome infection and/or the extent and type of bacterial infection that frequently accompanies this disease.