MicroRNA profiling of primary pulmonary enteric adenocarcinoma in members from the same family reveals some similarities to pancreatic adenocarcinoma—a step towards personalized therapy

Clinical Epigenetics

Elisa Giovannetti⁷  Guido Biasco⁶  Adam Enver Frampton³  Giampaolo Gavelli⁴  Giovanni Luca Frassineti¹  Massimo Negrini²  Manuela Ferracin²  Valentina Agostini⁵  Michelangelo Fiorentino⁵  Niccola Funel⁷  Ingrid Garajová⁶ 

[1] Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via Piero Maroncelli 40, Meldola, 47014, Italy;Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara, 44121, Italy;HPB Surgical Unit, Department of Surgery & Cancer, Hammersmith Hospital Campus, Imperial College, Du Cane Road, London W12 0HS, UK;Department of Radiology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via Piero Maroncelli 40, Meldola, 47014, Italy;Department of Pathology, F. Addari Institute, S.Orsola Malpighi Hospital, University of Bologna, Viale Ercolani 4/2, Bologna, 40138, Italy;Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, Bologna, 40138, Italy;Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Lungarno Pacinotti 43, Pisa, 56126, Italy

关键词: PEAC;    Immunohistochemistry;    Intestinal;    Enteric;    Pulmonary adenocarcinoma;   

Others  :  1235002
DOI  :  10.1186/s13148-015-0162-5

 received in 2015-10-13, accepted in 2015-12-07,  发布年份 2015

【 摘 要 】

Background

Primary pulmonary enteric adenocarcinoma (PEAC) is defined as a pulmonary adenocarcinoma with a predominant component of intestinal differentiation and tumor cells positive for at least one intestinal marker. The aim of the present study was the molecular and histological characterization of a PEAC from a patient with two other family members affected by similar lung tumors, which has never been reported before.

Findings

We evaluated the molecular characteristics of the proband’s PEAC by using a previously validated 47-microRNA (miRNA) cancer-specific array and a predictive method to estimate tissue-of-origin probabilities. Immunohistochemical (IHC) staining for thyroid transcription factor (TTF-1), napsin A, caudal-related homeobox 2 (CDX2), cytokeratins, and mucins, as well as mutational analyses for epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and anaplastic lymphoma kinase (ALK) were performed on formalin-fixed, paraffin-embedded (FFPE) tissues.

The occurrence of PEAC in two family members was associated with similar clinicopathological features (age at diagnosis, smoking habit, tumor localization, multiple colonic polyps), histologic findings (TTF-1 negativity and CDX2 positivity), and genetic findings (KRAS (Gly12Asp) mutation, but no EGFR/ALK aberrations). miRNA profiling revealed similarities with non-small cell lung cancer (NSCLC; 75.98 %) and some overlap with pancreatic ductal adenocarcinoma (PDAC; 23.34 %), but not with colorectal cancer (CRC; less than 0.5 %). Notably, these PEACs share key PDAC-associated miRNAs associated with tumor aggressiveness (miR-31*/-126*/-506/-508-3p/-514).

Conclusions

We describe for the first time PEAC in members from the same family, associated with similar clinical and genetic features. miRNA profiling of the PEAC resembled a NSCLC signature, with partial overlap to a PDAC pattern. This could explain its aggressive behavior and therefore help to guide future tailored-therapeutic approaches.

【 授权许可】

   
2015 Garajová et al.

【 图 表 】

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【 参考文献 】

• [1]Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, et al.: American Thoracic Society. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011, 6:244-85.
• [2]Tsao MS, Fraser RS: Primary pulmonary adenocarcinoma with enteric differentiation. Cancer 1991, 68(8):1754-7.
• [3]Inamura K, Satoh Y, Okumura S, Nakagawa K, Tsuchiya E, Fukayama M, et al.: Pulmonary adenocarcinomas with entric differentiation: histologic and immunohistochemical characteristics compared with metastatic colorectal cancers and usual pulmonary adenocarcinomas. Am J Surg Pathol 2005, 29(5):660-5.
• [4]Maeda R, Isowa N, Onuma H, Miura H: Pulmonary intestinal-type adenocarcinoma. Interact Cardiovasc Thorac Surg 2008, 7(2):349-51.
• [5]Li HC, Schmidt L, Greenson JK, Chang AC, Myers JL: Primary pulmonary adenocarcinoma with intestinal differentiation mimicking metastatic colorectal carcinoma: case report and review of literature. Am J Clin Pathol 2009, 13(1)):129-33.
• [6]Hatanaka K, Tsuta K, Watanabe K, Sugino K, Uekusa T: Primary pulmonary adenocarcinoma with enteric differentiation resembling metastatic colorectal carcinoma: a report of the second case negative for cytokeratin 7. Pathol Res Pract 2011, 207(3):188-91.
• [7]Lin D, Zhao Y, Li H, Xing X: Pulmonary enteric adenocarcinoma with villin brush border immunoreactivity: a case report and literature review. J Thorac Dis 2013, 5(1):E17-20.
• [8]Qureshi A, Furrukh M. Enteric adenocarcinoma lung: a rare presentation in an Omani woman. BMJ Case Rep 2013
• [9]László T, Lacza A, Tóth D, Molnár TF, Kálmán E: Pulmonary enteric adenocarcinoma indistinguishable from metastatic colorectal carcinoma morphologically and immunohistologically. Histopathology 2014, 65(2):283-7.
• [10]Wang CX, Liu B, Wang YF, Zhang RS, Yu B, Lu ZF, et al.: Pulmonary enteric adenocarcinoma: a study of the clinicopathologic and molecular status of nine cases. Int J Clin Exp Pathol 2014, 7(3):1266-74.
• [11]Stojsic J, Kontic M, Subotic D, Popovic M, Tomasevic D, Lukic J: Intestinal type of lung adenocarcinoma in younger adults. Case Rep Pulmonol 2014, 2014:282196.
• [12]Yousem SA: Pulmonary intestinal-type adenocarcinoma does not show enteric differentiation by immunohistochemical study. Mod Pathol 2005, 18(6):816-21.
• [13]El Hammoumi MM, El Ochi R, Kabiri EH. Primary lung adenocarcinoma with enteric morphology associated with primary colon adenocarcinoma. Arch Bronconeumol, 2015 [Epub ahead of print].
• [14]Rosenfeld N, Aharonov R, Meiri E, Rosenwald S, Spector Y, Zepeniuk M, et al.: MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol 2008, 26(4):462-9.
• [15]Ferracin M, Pedriali M, Veronese A, Zagatti B, Gafà R, Magri E, et al.: MicroRNA profiling for the identification of cancers with unknown primary tissue-of-origin. J Pathol 2011, 225(1):43-53.
• [16]Park C, Lee IJ, Jang SH, Lee JW: Factors affecting tumor recurrence after curative surgery for NSCLC: impacts of lymphovascular invasion on early tumor recurrence. J Thorac Dis 2014, 6(10):1420-8.
• [17]Permuth-Wey J, Chen YA, Fisher K, McCarthy S, Qu X, Lloyd MC, et al.: A genome-wide investigation of microRNA expression identifies biologically-meaningful microRNAs that distinguish between high-risk and low-risk intraductal papillary mucinous neoplasms of the pancreas. PLoS One 2015, 10(1):e0116869.
• [18]Frampton AE, Krell J, Jacob J, Stebbing J, Castellano L, Jiao LR: Loss of miR-126 is crucial to pancreatic cancer progression. Expert Rev Anticancer Ther 2012, 12(7):881-4.
• [19]Yin M, Ren X, Zhang X, Luo Y, Wang G, Huang K, et al.: Selective killing of lung cancer cells by miRNA-506 molecule through inhibiting NF-κB p65 to evoke reactive oxygen species generation and p53 activation. Oncogene 2014.
• [20]Sun Y, Hu L, Zheng H, Bagnoli M, Guo Y, Rupaimoole R, et al.: MiR-506 inhibits multiple targets in the epithelial-to-mesenchymal transition network and is associated with good prognosis in epithelial ovarian cancer. J Pathol 2015, 235(1):25-36.
• [21]Zhai Q, Zhou L, Zhao C, Wan J, Yu Z, Guo X, et al.: Identification of miR-508-3p and miR-509-3p that are associated with cell invasion and migration and involved in the apoptosis of renal cell carcinoma. Biochem Biophys Res Commun 2012, 419(4):621-6.
• [22]Garajová I, Le Large TY, Frampton AE, Rolfo C, Voortman J, Giovannetti E: Molecular mechanisms underlying the role of microRNAs in the chemoresistance of pancreatic cancer. Biomed Res Int 2014, 2014:678401.
• [23]Frampton AE, Giovannetti E, Jamieson NB, Krell J, Gall TM, Stebbing J, et al.: A microRNA meta-signature for pancreatic ductal adenocarcinoma. Expert Rev Mol Diagn 2014, 14(3):267-71.
• [24]Castellano-Megias VM, Ibarrola-de Andres C, Lopez-Alfonso G, Colina-Ruizdelgado F: Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas. World J Gastrointest Oncol 2014, 6(9):311-324.