Perianal Paget's disease (PPD) represents a skin neoplasm which can be either primary or secondary to carcinoma from an adjacent internal organ. PPD with underlying colorectal adenocarcinoma is usually looked upon as a secondary disease. We report a rare case of co-associated PPD and anorectal adenocarcinoma. The PPD was found to be located near the anorectal adenocarcinoma with normal tissues between them. Immunohistochemical stains demonstrated that the Paget's cells were CK7+/GCDFP-15-/CK20-/MUC2-/CDX2-, whereas the anorectal adenocarcinoma was shown to be CK7+/GCDFP-15-/CK20+/MUC2+/CDX2+. This immunological phenotypic profile supported the notion that PPD and anorectal adenocarcinoma were of different origins, but could not define the exact origins of PPD. In our determination, this case was a primary PPD with anorectal adenocarcinoma. PPD remains a heterogeneous and complex pathology, and additional studies are required to differentiate between the various possible origins.

Human phosphatidylethanolamine-binding protein 4(hPEBP4) is a novel anti-apoptosis molecule associated with the resistance of tumors to apoptotic agents. Here we sought to investigate the role of hPEBP4 in the radioresistance of rectal cancer. Immunohistochemistry analysis showed hPEBP4 was expressed in 27/33 of rectal cancer specimens, but only in 2/33 of neighboring normal mucosa. Silencing the expression of hPEBP4 with siRNA significantly reduced the clonogenic survival and enhanced the apoptosis of rectal cancer cells on irradiation. Instead, forced overexpression of hPEBP4 promoted its survival and decreased the apoptosis. Western blot showed hPEBP4 could increase the radiation-induced Akt activation, for which reactive oxygen specimen(ROS) was required. The radioresistance effect of hPEBP4 was reversed after given LY-294002 to inhibit Akt activation or antioxidant to abolish the ROS production. We also confirmed that effect of hPEBP4 in vivo with nude mice. Thus we concluded that hPEBP4, specifically expressed in rectal cancer cells, is associated with radioresistance of rectal cancer, implying that modulation of hPEBP4 may have important therapeutic implications in radiotherapy of rectal cancer.

BackgroundHuman phosphatidylethanolamine-binding protein 4 (hPEBP4) is a well-established antiapoptosis molecule in recent years. It has also been demonstrated to be involved in the radioresistance of rectal cancer. The objective of this study was to determine whether IOI-42, a chemical inhibitor of hPEBP4, could sensitize rectal cancer cells.MethodsRectal cancer cells were treated with IOI-42 alone or in combination with irradiation. Clonogenic survival assays and tumor volume growth analysis were used, respectively, to study the effect of IOI-42 in vitro and in vivo. Western blot was adopted to measure the activation of signal pathway.ResultsClonogenic survival assays showed that IOI-42, combined with irradiation, caused a significant decrease in colony formation compared with radiation alone, which was associated with the downregulation of Akt activation. And we also confirmed the effect of IOI-42 in nude mice transplanted with human rectal cancer subcutaneously.ConclusionsThese data suggest that IOI-42 has a potential to enhance the radiosensitivity of rectal cancer cells, providing a rationale to further investigate the feasibility of combining of IOI-42 with radiation, keeping in mind that this may result in unexpected toxicities.

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