Loss of SMAD4 staining in pre-operative cell blocks is associated with distant metastases following pancreaticoduodenectomy with venous resection for pancreatic cancer

Boone, Brian A.; Sabbaghian, Shirin; Zenati, Mazen S.; Marsh, J. Wallis; Moser, A. James; Zureikat, Amer H.; Singhi, Aatur D.; Zeh, Herbert J.; Krasinskas, Alyssa M.

doi:10.1002/jso.23606

Cited by 51 publications

(43 citation statements)

References 28 publications

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“…Recently, there have been encouraging trends in the oncologic management of stage III LAPC, with improved response rates to current chemotherapeutic combinations, 10,22 enhanced radiation delivery, 23,24 and enhancements in molecular marker diagnosis (KRAS, TP53, ACTN4, and SMAD4) [25][26][27] and, thus, potentially better prediction of underlying cancer biology. Current optimal systemic chemotherapy regimens that include either FOLFIRINOX-based chemotherapy or gemcitabine-Abraxane-based chemotherapy have enhanced response rates or improved PFS.…”

Section: Discussionmentioning

confidence: 99%

Treatment of 200 Locally Advanced (Stage III) Pancreatic Adenocarcinoma Patients With Irreversible Electroporation

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Treatment of 200 Locally Advanced (Stage III) Pancreatic Adenocarcinoma Patients With Irreversible Electroporation

et al. 2015

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“…16–21 In both tumor types, somatic inactivation of SMAD4 is accurately mirrored by loss of Smad4 protein expression by immunohistochemistry. 22,23 Smad4 immunohistochemistry has proven to be a valuable tool in delineating the role of SMAD4 in the pathogenesis of these tumors.…”

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confidence: 99%

Smad4 Loss in Esophageal Adenocarcinoma Is Associated With an Increased Propensity for Disease Recurrence and Poor Survival

Singhi

Foxwell

Nason

et al. 2015

American Journal of Surgical Pathology

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Previously regarded as a rare neoplasm, the incidence of esophageal adenocarcinoma has risen rapidly in recent decades. It is often discovered late in the disease process and has a dismal prognosis. Current prognostic markers including clinical, radiographic, and histopathologic findings have limited utility and do not consider the biology of this deadly disease. Genome-wide analyses have identified SMAD4 inactivation in a subset of tumors. Although Smad4 has been extensively studied in other gastrointestinal malignancies, its role in esophageal adenocarcinoma remains to be defined. Herein, we show, in a large cohort of esophageal adenocarcinomas, Smad4 loss by immunohistochemistry in 21 of 205 (10%) tumors and that Smad4 loss correlated with increased postoperative recurrence (P=0.040). Further, patients whose tumors lacked Smad4 had shorter time to recurrence (TTR) (P=0.007) and poor overall survival (OS) (P=0.011). The median TTR and OS of patients with Smad4-negative tumors was 13 and 16 months, respectively, as compared with 23 and 22 months, respectively, among patients with Smad4-positive tumors. In multivariate analyses, Smad4 loss was a prognostic factor for both TTR and OS, independent of histologic grade, lymphovascular invasion, perineural invasion, tumor stage, and lymph node status. Considering Smad4 loss correlated with postoperative locoregional and/or distant metastases, Smad4 was also assessed in a separate cohort of 5 locoregional recurrences and 43 metastatic esophageal adenocarcinomas. In contrast to primary tumors, a higher prevalence of Smad4 loss was observed in metastatic disease (44% vs. 10%). In summary, loss of Smad4 protein expression is an independent prognostic factor for TTR and OS that correlates with increased propensity for disease recurrence and poor survival in patients with esophageal adenocarcinoma after surgical resection.

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“…[87] In future SMAD4-intact disease may be identified as the one subgroup likely to benefit from locally aggressive therapy. [88] Immunotherapy in pancreatic cancers is also being explored Le et al [89] investigated the effect of administering CRS-207 with GVAX on overall survival in metastatic pancreatic cancer. GVAX consists of irradiated pancreatic cancer cells that have modified to elude granulocyte-macrophage colony-stimulating factor (GM-CSF) and produce an antitumour immune response.…”

Section: Futurementioning

confidence: 99%

Advances in Chemotherapy for Pancreatic Cancer

Sirohi

Singh

Dawood

et al. 2015

Indian J Surg Oncol

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Loss of SMAD4 staining in pre-operative cell blocks is associated with distant metastases following pancreaticoduodenectomy with venous resection for pancreatic cancer

Cited by 51 publications

References 28 publications

Treatment of 200 Locally Advanced (Stage III) Pancreatic Adenocarcinoma Patients With Irreversible Electroporation

Treatment of 200 Locally Advanced (Stage III) Pancreatic Adenocarcinoma Patients With Irreversible Electroporation

Smad4 Loss in Esophageal Adenocarcinoma Is Associated With an Increased Propensity for Disease Recurrence and Poor Survival

Advances in Chemotherapy for Pancreatic Cancer

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