High Smac/DIABLO expression is associated with early local recurrence of cervical cancer

Abstract

BackgroundIn a recent pilot report, we showed that Smac/DIABLO mRNA is expressed de novo in a subset of cervical cancer patients. We have now expanded this study and analyzed Smac/DIABLO expression in the primary lesions in 109 cervical cancer patients.MethodsWe used immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections to analyze Smac/DIABLO expression in the 109 primary lesions. Seventy-eight samples corresponded to epidermoid cervical cancer and 31 to cervical adenocarcinoma. The median follow up was 46.86 months (range 10–186).ResultsSmac/DIABLO was expressed in more adenocarcinoma samples than squamous tumours (71% vs 50%; p = 0.037). Among the pathological variables, a positive correlation was found between Smac/DIABLO immunoreactivity and microvascular density, a marker for angiogenesis (p = 0.04). Most importantly, Smac/DIABLO immunoreactivity was associated with a higher rate of local recurrence in squamous cell carcinoma (p = 0.002, log rank test). No association was found between Smac/DIABLO and survival rates.ConclusionSmac/DIABLO expression is a potential marker for local recurrence in cervical squamous cell carcinoma patients.

Role of Smac in Determining the Chemotherapeutic Response of Esophageal Squamous Cell Carcinoma

“…Thus, Smac downregulation may contribute to esophageal carcinogenesis. Reduced Smac expression has also been described in other types of cancer (11,38,(40)(41)(42). Importantly, our data revealed a significant association between Smac expression and chemotherapeutic response among the 31 ESCC patients who had undergone chemotherapy.…”

Prognostic significance of smac/DIABLO in endometrioid endometrial cancer.

“…Thus, alteration of apoptosis is essential for cancer development and cancer cell death by radiation and chemotherapy is largely dependent upon apoptosis [16]. These data partially contradict those of others that smac/DIABLO expression does not correlate with stage, grade and prognosis [20,21].…”

Smac/DIABLO is required for effector caspase activation during apoptosis in human cells

“…The members of the inhibitor of apoptosis (IAP) protein family are highly expressed in several classes of cancer. Interestingly, recent studies revealed that Smac is also differentially expressed in cervical tumors and in tumor cell lines [19,20]. These observations have prompted researchers to design Smac mimetic compounds that can be administered either alone or in combination with other chemotherapeutic agents to kill tumor cells.…”