• DNA analysis by flow cytometry, response to endocrine treatment and prognosis in advanced carcinoma of the breast.

      Baildam, Andrew D; Zaloudik, J; Howell, Anthony; Barnes, Diana M; Turnbull, Lesley; Swindell, Ric; Moore, Michael; Sellwood, R A (1987-05)
      The relationship between DNA content of mammary cancer and subsequent response to endocrine therapy was studied in 136 patients with advanced disease. All were treated with tamoxifen or ovarian ablation as first-line systemic therapy after relapse and were evaluable for response according to UICC criteria. DNA characterisation by flow cytometry was used on formalin fixed paraffin-embedded samples of tumour. Tumours were grouped according to DNA index into diploid (n = 52, 38%), 'tetraploid' (n = 46, 34%) and 'other DNA-aneuploid' (n = 38, 28%). The highest proportion of oestrogen receptor positive tumours (ER + ve) was found in the 'tetraploid' tumours (38/46, 85%, Chi-square = 8.53, P less than 0.02), and response rates, (SD + PR + CR), were 26/52 (50%), 34/46 (74%), and 15/38 (39%) respectively (Chi-square = 10.88, P less than 0.005). Patients with diploid or 'tetraploid' tumours survived longer and stayed in remission longer than those with 'other DNA-aneuploid' tumours. We suggest that 'tetraploid' or 'near tetraploid' human mammary tumours may comprise a distinct group of endocrine responsive tumours within the overall group of aneuploid tumours. The conventional interpretation of DNA histograms, grouping into diploid and aneuploid, may be masking important features of some tumour groups.
    • DNA content and MHC class II antigen expression in malignant melanoma: clinical course.

      Zaloudik, J; Moore, Michael; Ghosh, Anna K; Mechl, Z; Rejthar, A; Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital, Manchester. (1988-10)
      To assess the clinical value of two comparatively new properties (DNA content and MHC class II antigen expression (HLA-DR, DP, DQ) of melanoma cells) which have been independently reported to reflect the outlook for patients with malignant melanoma, we investigated retrospectively 50 stage I nodular melanomas in two comparably homogeneous groups of 23 and 27 patients, the course of whose disease differed at five years. Flow cytometry and immunohistology were used on paraffin wax embedded archival material for the analysis of DNA ploidy and detection of class II antigens, respectively. A close association was found between class II antigen expression, detected by monoclonal antibody CR3/43 (antimonomorphic DR, DP, DQ) present in 23 of 50 (46%) melanomas and unfavourable clinical course (p less than 0.005, by log rank test), but no such association was found for DNA ploidy. It is suggested that immunohistology for MHC class II antigen expression may help to predict the behaviour of nodular melanomas whereas the prognostic value of DNA ploidy is more limited. The finding that class II positive cells are found predominantly in melanomas with a substantially increased risk of metastases has implications both for concepts of tumour heterogeneity and host immunity.
    • The DNA content of colorectal carcinomas: an analysis of the heterogeneity of aneuploidy and correlation with immunopathological parameters.

      Zaloudik, J; Moore, Michael; Hasleton, Philip S; Research Institute of Clinical and Experimental Oncology, Brno, Czechoslovakia. (1988)
      DNA ploidy patterns of 107 colorectal adenocarcinomas were retrospectively analyzed by flow cytometry (FCM) and correlated with clinicopathological and immunohistological parameters as grade, vascular and serosal invasion, carcinoembryonic antigen, secretory component (SC) and expression of HLA-DR antigens. Using the classical division into DNA diploid and DNA aneuploid tumors, a correlation with SC expression was observed. Subdivision of aneuploid tumors according to the discussed hypothetical functional criteria into hyperdiploid, hypotetraploid, tetraploid and hypertetraploid groups led to statistically significant correlation with serosal invasion. Among the immunohistological parameters the interdependence of SC and HLA-DR expression may be also of interest. The need for subdivision of DNA aneuploidy is broadly discussed so as to permit the analysis of different properties, cellular origins and kinetic parameters. Ultimately this may lead to more clinically meaningful interpretation of DNA histograms.
    • Effect of tamoxifen upon cell DNA analysis by flow cytometry in primary carcinoma of the breast.

      Baildam, Andrew D; Zaloudik, J; Howell, Anthony; Barnes, Diana M; Moore, Michael; Sellwood, R A (1987-05)
      The effect of tamoxifen upon cellular DNA ploidy in carcinoma of the breast was assessed by flow cytometry (FCM), in a prospective group of 77 patients with primary operable disease. Each had a needle biopsy at the outpatient visit for diagnosis and FCM analysis, and definitive surgery was performed a median of 8 days later. Forty received tamoxifen during this period - 40 mg qds loading dose for 24 h, followed by 20 mg daily until the day of operation: 37 patients received no therapy. The DNA histogram from the needle biopsy was compared with that obtained from the resected tumour for each individual. There was little change between the pair of histograms from tumours from the untreated patients. In those who had received tamoxifen the most consistent effect was a marked reduction in the magnitude of the 'tetraploid' peak in tetraploid or near-tetraploid tumours with DNA indices 1.8-2.0. There was little change in diploid or 'other DNA-aneuploid' tumours. In tetraploid tumours (DNA index of 2.0) the percentage of nuclei in the diploid S phase was significantly related to the percentage of nuclei in the diploid G2 + M/tetraploid G1 peak (P less than 0.003, unpaired t test). These data suggest that an effect of tamoxifen can be demonstrated by FCM upon tumours exhibiting a tetraploid or near-tetraploid DNA content. It is possible that tetraploid or near-tetraploid human mammary tumours may be a distinct group of endocrine responsive tumours within the overall group of aneuploid tumours, and that the majority are probably derived from the diploid population rather than being a true aneuploid population.
    • Predicting local recurrence of carcinoma of the rectum after preoperative radiotherapy and surgery.

      Jones, D J; Zaloudik, J; James, Roger D; Haboubi, N; Moore, M; Schofield, Philip F; Department of Surgery, Christie Hospital and Holt Radium Institute, Manchester, UK. (1989-11)
      A prospective study of prognostic factors has been carried out in a group of 186 patients with tethered rectal carcinomas. Of these, 97 were randomized to surgery alone and 89 to receive preoperative radiotherapy (20 Gy in four fractions). DNA ploidy was determined by flow cytometry. DNA aneuploidy was detected in 60 patients (62 per cent) in the surgery only group, but in only 33 patients (37 per cent) after radiotherapy (P less than 0.01). There was a significant reduction in local recurrence in irradiated patients (P less than 0.0001). DNA diploid tumours were less likely to recur locally. This was more marked in the radiotherapy group (P = 0.01) than in the surgery only group (P = 0.06). After radiotherapy, only the surgeons' assessments of a 'curative' resection and DNA ploidy were independent predictors of local recurrence in multivariate regression analysis, whilst Dukes' classification was not. In conclusion, DNA ploidy may indicate response to radiotherapy and is an important predictor of subsequent local tumour progression.