Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas.

Affiliation

Vanoli A(1), Grillo F(2), Guerini C(3), Neri G(3), Arpa G(3), Klersy C(4), Nesi G(5), Giuffrida P(6), Sampietro G(7), Ardizzone S(8), Fociani P(9), Fiocca R(2), Latella G(10), Sessa F(11), D'Errico A(12), Malvi D(12), Mescoli C(13), Rugge M(13), Ferrero S(14), Poggioli G(15), Rizzello F(16), Macciomei MC(17), Santini D(12), Volta U(18), De Giorgio R(19), Caio G(19), Calabrò A(20), Ciacci C(21), D'Armiento M(22), Rizzo A(23), Solina G(24), Martino M(6), Tonelli F(25), Villanacci V(26), Cannizzaro R(27), Canzonieri V(28)(29), Florena AM(30), Biancone L(31), Monteleone G(31), Caronna R(32), Ciardi A(33), Elli L(34), Caprioli F(34), Vecchi M(34), D'Incà R(35), Zingone F(35), D'Odorico A(35), Lenti MV(6), Oreggia B(36), Reggiani Bonetti L(37), Giannone AG(30), Orlandi A(38), Barresi V(39), Ciccocioppo R(40), Amodeo G(40), Biletta E(41), Luinetti O(3), Pedrazzoli P(6)(42), Pietrabissa A(43), Corazza GR(6), Solcia E(3), Paulli M(3), Di Sabatino A(6).
Author information:
(1)Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy. [Email]
(2)Pathology Unit, Department of Surgical and Diagnostic Sciences, University of Genoa and Ospedale Policlinico San Martino University Hospital, Genoa, Italy.
(3)Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.
(4)Clinical Epidemiology and Biometry Unit, Fondazione IRCCS San Matteo Hospital, Pavia, Italy.
(5)Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
(6)Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.
(7)Unit of General Surgery, ASST Rhodense, Rho Hospital, University of Milan, Milan, Italy.
(8)Gastroenterology Unit, Luigi Sacco University Hospital, Milan, Italy.
(9)Anatomic Pathology Unit, ASST Ovest Milanese, Milan, Italy.
(10)Gastroenterology Unit, Department of Life and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
(11)Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
(12)Department of Experimental, Diagnostic and Specialty Medicine
(DIMES), Institute of Oncology and Transplant Pathology, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
(13)Pathology Unit, Department of Medicine, University of Padua, Padua, Italy.
(14)Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
(15)Surgery of the Alimentary Tract, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
(16)Intestinal Chronic Bowel Disease Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
(17)Pathology Unit, San Camillo-Forlanini Hospital, Rome, Italy.
(18)Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
(19)Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
(20)Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
(21)Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
(22)Public Health Department, Federico II University of Naples, Naples, Italy.
(23)Unit of Pathology, Cervello Hospital, Palermo, Italy.
(24)Units of General Surgery, Cervello Hospital, Palermo, Italy.
(25)Surgery and Translational Medicine, University of Florence, Florence, Italy.
(26)Institute of Pathology, Spedali Civili Hospital, Brescia, Italy.
(27)Department of Gastroenterology, Centro di Riferimento Oncologico
(CRO) di Aviano IRCCS, Aviano, Italy.
(28)Pathology Unit, Centro di Riferimento Oncologico
(CRO) di Aviano IRCCS, Aviano, Italy.
(29)Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
(30)Pathologic Anatomy Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
(31)Department of Systems Medicine, University of Tor Vergata, Rome, Italy.
(32)Department of Surgical Sciences, La Sapienza University, Rome, Italy.
(33)Department of Radiological, Oncological, Pathological Sciences, Umberto I Hospital, La Sapienza University, Rome, Italy.
(34)Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
(35)Gastroenterology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
(36)General Surgery Unit, Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.
(37)Section of Pathology, Department of Diagnostic Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy.
(38)Department of Biopathology and Image Diagnostics, University of Tor Vergata, Rome, Italy.
(39)Section of Anatomical Pathology, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy.
(40)Gastroenterology Unit, Department of Medicine, AOUI Policlinico G.B. Rossi, University of Verona, Verona, Italy.
(41)Anatomic Pathology ASL Biella, Biella, Italy.
(42)Oncology Unit, IRCCS San Matteo Hospital, Pavia, Italy.
(43)Department of Surgery, General Surgery II, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.

Abstract

BACKGROUND: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer. PATIENTS AND METHODS: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability. RESULTS: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status. CONCLUSIONS: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.