Another interesting study is called, “Value of the Mesothelium-Associated Antibodies Thrombomodulin, Cytokeratin 5/6, Calretinin, and CD44H in Distinguishing Epithelioid Pleural Mesothelioma from Adenocarcinoma Metastatic to the Pleura” by P M Cury M.D., D N Butcher, C Fisher M.D., B Corrin M.D. and A G Nicholson D.M. – Mod Pathol 2000;13(2):107–112. Here is an excerpt: “Abstract – Until recently, the standard approach of most laboratories in distinguishing epithelioid pleural mesothelioma from metastatic adenocarcinoma has been a negative result from a panel of adeno-carcinoma-associated antibodies. However, several “mesothelium-associated” antibodies have been proposed as useful in this situation, and we have applied four of these putative mesothelioma markers—thrombomodulin, cytokeratin 5/6, calretinin, and CD44H—to a series of 61 epithelioid pleural mesotheliomas and 63 metastatic adenocarcinomas with known primary sites (lung = 19; breast = 21; ovary = 6; colon = 10; kidney = 4; uterus, epididymis, pancreas = 1 case each). Of the mesotheliomas, 55 of 61 (90%) stained for thrombomodulin, 56 of 61 (92%) for cytokeratin 5/6, 47 of 51 cases (92%) were positive for calretinin, and 39 of 43 (91%) were positive for CD44H. Of the metastatic adenocarcinomas, 12 of 63 (19%) cases were positive for thrombomodulin, 9 of 63 (14%) were positive for CK5/6, and 27 of 60 (45%) were positive for CD44H. With calretinin, only 1 case of 59 (2%) showed positive nuclear staining. All four antibodies stained reactive mesothelium; thrombomodulin also stained endothelium; and CD44H variably stained lymphocytes, macrophages, and fibroblasts. We conclude that all four antibodies show high sensitivity for epithelioid mesothelioma, but only calretinin (98%), cytokeratin 5/6 (86%), and thrombomodulin (81%) show sufficient specificity for practical use in this situation.”
Another interesting study is called, “Surgical treatment of pleural Mesothelioma” by PM McCormack, F Nagasaki, BS Hilaris and N Martini – The Journal of Thoracic and Cardiovascular Surgery, Vol 84, 834-842. Here is an excerpt: “From 1939 through 1981, 170 patients were seen and treated for pleural mesothelioma. Twenty-one tumors were benign, 47 were fibrosarcomatous, and 102 were epithelioma. Resection was the main mode of treatment in benign and fibrosarcomatous mesothelioma. Treatment of diffuse epithelial mesothelioma presented the greatest challenge. Surgical therapy, radiation therapy, and chemotherapy were used in combination in these patients. The review of our patients treated prior to 1972 had shown no benefit from including pulmonary resection in the surgical treatment of these tumors. Since then, all patients with diffuse mesothelioma were treated by pleurectomy without pulmonary resection. Both internal and external radiation therapy were also used to enhance local control. Forty-nine percent of patients with epithelial mesothelioma lived 1 year. The median survival in patients whose disease was controlled by these methods was 21 months. Despite the poor prognosis in malignant mesothelioma, better controlled by these methods was 21 months. .”
Another interesting study is called, “RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulmonary small cell carcinoma, and mesothelioma.” By Shimizu E, Coxon A, Otterson GA, Steinberg SM, Kratzke RA, Kim YW, Fedorko J, Oie H, Johnson BE, Mulshine JL, et al. – National Cancer Institute-Navy Oncology Branch, National Cancer Institute, Bethesda, Maryland 20889. – Oncogene. 1994 Sep;9(9):2441-8. Here is an excerpt: “Abstract – We have studied RB protein expression in 171 cell lines derived from patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), pulmonary carcinoid, mesothelioma, and extrapulmonary small cell cancer (EPSC) and have correlated this data with clinical outcome. We detected absent or aberrant RB protein expression in 66/75 SCLC, 12/80 NSCLC, 1/6 carcinoid, 0/5 mesothelioma, and 4/5 EPSC samples. In addition, we observed integration of human papilloma virus (HPV) DNA in the single EPSC cell line that retained wildtype RB protein. We did not detect integration of HPV, SV40 or adenoviral DNA in other tumor samples with wildtype RB status. We also noted a stable, hypophosphorylated mutant RB in 12 SCLC and 3 NSCLC samples which might have been falsely interpreted as wildtype by current immunohistochemical techniques. Analysis of the matched clinical data showed no associations between RB status and age, sex, extent of disease, performance status, smoking history, and previous treatment. In addition, retrospective analyses showed no consistent correlation of RB protein expression with either best clinical response, overall survival, or in vitro chemotherapeutic drug sensitivity. The stable expression of RB after gene transfection into RB(-) SCLC cells, however, resulted in a trend toward increased in vitro resistance to etoposide, cisplatin and doxorubicin.”
We all owe a debt of gratitude to these fine researchers. If you found any of these excerpts interesting, please read the studies in their entirety.