Mesothelioma and Antibodies to Epithelial Membrane Antigen

Mesothelioma and Antibodies to Epithelial Membrane Antigen

One interesting study is called, “The use of histological and immunohistochemical markers to distinguish pleural malignant mesothelioma and in situ mesothelioma from reactive mesothelial hyperplasia and reactive pleural fibrosis” by P. M. Cury, D. N. Butcher, B. Corrin, A. G. Nicholson – The Journal of Pathology Volume 189, Issue 2, pages 251–257, October 1999.  Here is an excerpt: “Abstract – Distinguishing malignant mesothelioma from reactive mesothelial hyperplasia and reactive fibrosis can be a diagnostic problem in small pleural biopsies, made more difficult by the recent recognition of mesothelioma-in-situ. Antibodies to epithelial membrane antigen (EMA), p53, and bcl-2 have all been advocated for differentiating reactive from neoplastic conditions, but reports are inconsistent. These antibodies have therefore been applied to 31 cases of malignant mesothelioma, 34 cases of reactive pleural disease (20 reactive mesothelial hyperplasia and 14 reactive pleural fibrosis) and four small biopsies that were initially coded as suspicious, from patients who later developed frank mesothelioma. Thirty out of 31 (97 per cent) cases of mesothelioma showed positive nuclear staining for p53, with a higher incidence of positivity in epithelioid than in sarcomatoid elements and 30/31 (97 per cent) showed diffuse linear membrane staining for EMA, again more intense in the epithelioid elements. No mesothelioma was positive for bcl-2. In seven cases that contained both in situ and invasive mesothelioma, the in situ elements showed similar staining patterns to the invasive epithelioid elements. Thirteen out of 20 (65 per cent) cases of reactive mesothelial hyperplasia showed occasional nuclear positivity for p53 and 5/20 (25 per cent) cases showed focal weak membrane staining for EMA. Three out of 14 (21 per cent) cases of reactive pleural fibrosis showed positive nuclear staining for p53 and 6/14 (43 per cent) cases showed focal membrane staining with EMA. No reactive cases stained for bcl-2. All four suspicious cases showed diffuse linear staining with EMA and three showed focal staining for p53. It is concluded that strong diffuse linear staining for EMA is a good marker of malignancy when differentiating epithelioid malignant mesothelioma and mesothelioma-in-situ from reactive mesothelial hyperplasia, although weak focal staining may occur in reactive conditions. Nuclear staining for p53 is also suggestive of epithelioid mesothelioma, but should be regarded as no more than suspicious. The antibodies used in this investigation are less helpful in differentiating sarcomatoid mesothelioma from reactive pleural fibrosis.”

Another interesting study is called, “Effusion cytology in the diagnosis of malignant epithelioid and biphasic pleural mesothelioma.” Arch Pathol Lab Med. 1990 Aug;114(8):845-51 by Sherman ME, Mark EJ – James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston.  Here is an excerpt: “Abstract –
We reviewed the cytologic findings in pleural effusions of 36 patients in whom a diffuse epithelioid or biphasic malignant mesothelioma of the pleura developed between 1978 and 1988. Malignant neoplasms were diagnosed in 26 (72%) of the 36 patients. A specific diagnosis of a mesothelioma was rendered or suspected in 64% (23/36 patients). Mesothelioma was favored over adenocarcinoma in 81% (29/36) of patients with positive fluid cytologic findings. The contribution of effusion cytology to the final diagnosis and patient treatment was assessed. These data suggested that a cytologic diagnosis contributed useful information in most patients with malignant epithelioid and biphasic pleural mesotheliomas.”

Another interesting study is called, “A randomised trial in malignant mesothelioma (M) of early (E) versus delayed (D) chemotherapy in symptomatically stable patients: the MED trial” by M. E. R. O’Brien, D. Watkins, C. Ryan, K. Priest, C. Corbishley, A. Norton, S. Ashley, N. Rowell  and R. Sayer – Ann Oncol (February 2006) 17 (2): 270-275.   Here is an excerpt: “Abstract – Background: Prior phase II trials have demonstrated the therapeutic activity of cytotoxic chemotherapy in mesothelioma. Currently there are few randomised data assessing the role of chemotherapy versus best supportive care (BSC) in the management of patients with stable symptoms after control of any pleural effusion. A policy of observation is often adopted over initial use of chemotherapy. In this prospective randomised trial we assess the use of early versus delayed cytotoxic therapy. The study opened in 1998, and closed in view of a competing national study (MSO 1) in 2003.   Methods: Eligible patients had a performance status ≤2, life expectancy >3 months and had stable symptoms for at least 4 weeks prior to randomisation. Patients were randomised to receive immediate chemotherapy or initial BSC with the addition of chemotherapy at time of symptomatic progression. All patients received the same platinum-based chemotherapy regimen, MVP [mitomycin C 8 mg/m2 cycles 1, 2, 4 and 6, vinblastine 6 mg/m2, maximum 10 mg, and cisplatin 50 mg/m2 (or carboplatin AUC 5)], every 3 weeks for up to six cycles.   Results: A total of 43 patients were recruited, of which 21 were randomised to the early treatment group and 22 to the delayed treatment group. The median ages were 59 years (range 50–78) and 67 years (range 48–75), respectively (P = 0.1); other baseline parameters were well matched between the two groups. All 21 patients in the early group received chemotherapy versus 17 patients in the delayed group. Median time to symptomatic progression was 25 weeks in the early group compared with 11 weeks for the delayed group (P = 0.1). Median survival was 14 months (1-year survival 66%) for the early group compared with 10 months (1-year survival 36%) for the delayed group (P = 0.1). Quality of life was in general better maintained for early treatment and the health resources use was similar in both arms.   Conclusions: In this patient group, presenting with stable symptoms after control of pleural effusion, the early use of chemotherapy provided an extended period of symptom control, and in this small trial a trend to survival advantage.”

Monty Wrobleski is the author of this article.  For more information please click on the following links

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