Differential Expression of Ki-67 and Sex Steroid Hormone Receptors Between Genders in Peritoneal Mesothelioma

Abstract

Gender influence on survival in mesothelioma has been observed in several large clinical series. However, this gender effect has not been investigated. Female patients often have less aggressive tumors and survive longer. However, few studies in the literature have explained the molecular basis of this finding. Understanding this difference at a molecular level may offer the hope of improving survival via hormonal manipulation.We investigate the expression of Ki-67 and sex steroid receptors; estrogen receptors (ER), progesterone receptors (PR) and androgen receptors (AR) to elucidate any pathognomonic difference that characterize this gender difference. Positive expression of markers was observed in 95% (Ki-67), 80% (ER), 100% (PR) and 65% (AR) of patients. Expression of markers between gender showed a higher Ki-67 in males (M = 1.3%, F = 0.6%), higher estrogen receptor in females (M = 0.6%, F = 1.7%) and higher progesterone receptor in females (M = 1.0%, F = 1.4%). Twenty patients were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in our peritonectomy unit. Paraffin sections of the tumor specimens were retrieved for immunohistochemical analysis. The immunostaining was performed using monoclonal mouse anti-human antibodies on an autostainer (Autostainer Plus; Dako, Inc.). The intensity of the stains were quantified using the Image-Pro Plus (IPP) 4.5 (Media Cybernetics, Silver Spring, MD). For the first time, we demonstrate the presence of sex steroid receptors in peritoneal mesothelioma. Once the exact functional effects of these receptors are understood, the use of established therapeutic options that are clinically available to target the sex steroid pathway may become a reality.

Cyclooxygenase-2, Epidermal Growth Factor Receptor, and Aromatase Signaling in Inflammation and Mesothelioma

“…This seeming discrepancy may be due to different types of exposure to the carcinogen. Recently, sex steroid receptors have been found in peritoneal mesothelioma (76).…”

Multicystic mesothelioma has malignant potential: its grounds and mechanisms of peritoneal metastasis

“…MIB-1 index of diffuse peritoneal mesothelioma is reported to range from 0.6% to 10%. [10][11][12] MIB-1 index higher than cutoff level in diffuse peritoneal mesothelioma correlates with poor outcome. In contrast, MIB-1 indices were low in the present 9 cases, These results may indicate that MCPM has malignant potential with low proliferative activity.…”

Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

“…Immunohistochemical staining with Ki-67 of Mib-1 antibodies is an excellent marker of cellular proliferation and tumour aggressiveness. [30] Three independent studies showed low Ki-67 expression in peritoneal mesothelioma, with a median of 0.6% to 10% positive cells. (13,(29)(30)).…”

“…[30] Three independent studies showed low Ki-67 expression in peritoneal mesothelioma, with a median of 0.6% to 10% positive cells. (13,(29)(30)). Analogously, mitotic rate is gerally low in malignant peritoneal mesothelioma, but higher proliferative activity correlates with poor outcome.…”