Skip to main content
Cancer Biomarkers: Section A of Disease Markers logoLink to Cancer Biomarkers: Section A of Disease Markers
. 2016 Apr 13;16(4):569–574. doi: 10.3233/CBM-160599

Anaplastic lymphoma kinase (ALK) gene alteration in gastric signet ring cell carcinoma

Ruihua Zhao a, Wenjing Jiang a, Xiangke Li a, Weijie Zhang a, Lijie Song a, Zhiwei Chang a, Wei Cao d, Xinguang Cao b,c,*, Hong Zong a,*
PMCID: PMC13016512  PMID: 27002760

Abstract

BACKGROUND:

This study was aimed to investigating the frequency of Anaplastic lymphoma kinase (ALK) alterations in patients with gastric signet ring cell carcinoma (SRC) and the correlations between ALK alterations and the clinical-pathological features.

METHODS:

The expression of ALK protein was first determined in paraffin-embedded tissue specimens (FFPE) from 177 pathologically confirmed SRC patients by Ventana Immunohistochemistry (IHC). Then patients with ALK positive detected by IHC were assayed in ALK rearrangement by Fluorescence in Situ Hybridization (FISH).

RESULTS:

We assessed 4 of 177 cases (2.3%) as positive by IHC. 3 of the 4 patients had T4 tumors and positive nodal status, and 1 of them had metastasis. All of them were HER2 negative. All of the 4 patients were positive for ALK rearrangement using the standard criteria of FISH.

COUCLUSION:

Our analysis showed that about 2.3% of Chineses SRC patients treated in our hospital were ALK positive. Ventana IHC and FISH were both of the reliable approaches in SRC patients. Patients with ALK positive seemed to have deep infiltrated and positive lymph nodes and HER2 negative.

Keywords: Anaplastic lymphoma kinase (ALK), signet ring cell carcinoma (SRC), gastric cancer

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

References

  • [1]. Siegel R., Ma J., Zou Z., and Jemal A., Cancer statistics, 2014. CA Cancer J Clin 64 (2014) 9-29. [DOI] [PubMed] [Google Scholar]
  • [2]. Karimi P., Islami F., Anandasabapathy S., Freedman N.D., and Kamangar F., Gastric cancer: Descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev 23 (2014) 700-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [3]. Piessen G., Messager M., Le Malicot K., Robb W.B., Di Fiore F., Guilbert M., Moreau M., Christophe V., Adenis A., and Mariette C., Phase II/III multicentre randomised controlled trial evaluating a strategy of primary surgery and adjuvant chemotherapy versus peri-operative chemotherapy for resectable gastric signet ring cell adenocarcinomas - PRODIGE 19 - FFCD1103 - ADCI002. BMC Cancer 13 (2013) 281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4]. Piessen G., Messager M., Leteurtre E., Jean-Pierre T., and Mariette C., Signet Ring Cell Histology is an Independent Predictor of Poor Prognosis in Gastric Adenocarcinoma Regardless of Tumoral Clinical Presentation. Annals of Surgery 250 (2009) 878-887. [DOI] [PubMed] [Google Scholar]
  • [5]. Morris S.W., Kirstein M.N., Valentine M.B., Dittmer K.G., Shapiro D.N., Saltman D.L., and Look A.T., Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 263 (1994) 1281-4. [DOI] [PubMed] [Google Scholar]
  • [6]. Soda M., Choi Y.L., Enomoto M., Takada S., Yamashita Y., Ishikawa S., Fujiwara S., Watanabe H., Kurashina K., Hatanaka H., Bando M., Ohno S., Ishikawa Y., Aburatani H., Niki T., Sohara Y., Sugiyama Y., and Mano H., Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448 (2007) 561-6. [DOI] [PubMed] [Google Scholar]
  • [7]. Shaw A.T., Solomon B., and Kenudson M.M., Crizotinib and testing for ALK. J Natl Compr Canc Netw 9 (2011) 1335-41. [DOI] [PubMed] [Google Scholar]
  • [8]. Kwak E.L., Bang Y.J., Camidge D.R., Shaw A.T., Solomon B., Maki R.G., Ou S.H., Dezube B.J., Janne P.A., Costa D.B., Varella-Garcia M., Kim W.H., Lynch T.J., Fidias P., Stubbs H., Engelman J.A., Sequist L.V., Tan W., Gandhi L., Mino-Kenudson M., Wei G.C., Shreeve S.M., Ratain M.J., Settleman J., Christensen J.G., Haber D.A., Wilner K., Salgia R., Shapiro G.I., Clark J.W., and Iafrate A.J., Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 363 (2010) 1693-703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [9]. Rodig S.J., Mino-Kenudson M., Dacic S., Yeap B.Y., Shaw A., Barletta J.A., Stubbs H., Law K., Lindeman N., Mark E., Janne P.A., Lynch T., Johnson B.E., Iafrate A.J., and Chirieac L.R., Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res 15 (2009) 5216-23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10]. Foltyn W, Zaj?cki W, Marek B, Kajdaniuk D, Siemińska L, Zemczak A, Kos-Kudƚa B, The value of the Ki-67 proliferation marker as a prognostic factor in gastroenteropancreatic neuroendocrine tumours. Endokrynol Pol 63 (2012) 5. [PubMed] [Google Scholar]
  • [11]. Ying J., Guo L., Qiu T., Shan L., Ling Y., Liu X., and Lu N., Diagnostic value of a novel fully automated immunochemistry assay for detection of ALK rearrangement in primary lung adenocarcinoma. Ann Oncol 24 (2013) 2589-93. [DOI] [PubMed] [Google Scholar]
  • [12]. Fu S., Wang H.Y., Wang F., Huang M.Y., Deng L., Zhang X., Ye Z.L., and Shao J.Y., Clinicopathologic characteristics and therapeutic responses of Chinese patients with non-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement. Chin J Cancer 34 (2015) 35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [13]. Chan B.A., and Hughes B.G., Targeted therapy for non-small cell lung cancer: Current standards and the promise of the future. Transl Lung Cancer Res 4 (2014) 36-54. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14]. Schneeweiss A., Ruckhaberle E., and Huober J., Chemotherapy for Metastatic Breast Cancer - An Anachronism in the Era of Personalised and Targeted Oncological Therapy? Geburtshilfe Frauenheilkd 75 (2015) 574-583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [15]. Oholendt A.L., and Zadlo J.L., Ramucirumab: A New Therapy for Advanced Gastric Cancer. J Adv Pract Oncol 6 (2015) 71-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [16]. Bang Y.J., Van Cutsem E., Feyereislova A., Chung H.C., Shen L., Sawaki A., Lordick F., Ohtsu A., Omuro Y., Satoh T., Aprile G., Kulikov E., Hill J., Lehle M., Ruschoff J., and Kang Y.K., Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 376 (2010) 687-97. [DOI] [PubMed] [Google Scholar]
  • [17]. Liao B.C., Lin C.C., Shih J.Y., and Yang J.C., Treating patients with ALK-positive non-small cell lung cancer: Latest evidence and management strategy. Ther Adv Med Oncol 7 (2015) 274-90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18]. Panagopoulos I., Nilsson T., Domanski H.A., Isaksson M., Lindblom P., Mertens F., and Mandahl N., Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor. Int J Cancer 118 (2006) 1181-6. [DOI] [PubMed] [Google Scholar]
  • [19]. Debelenko L.V., Raimondi S.C., Daw N., Shivakumar B.R., Huang D., Nelson M., and Bridge J.A., Renal cell carcinoma with novel VCL-ALK fusion: New representative of ALK-associated tumor spectrum. Mod Pathol 24 (2011) 430-42. [DOI] [PubMed] [Google Scholar]
  • [20]. Lin E., Li L., Guan Y., Soriano R., Rivers C.S., Mohan S., Pandita A., Tang J., and Modrusan Z., Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers. Mol Cancer Res 7 (2009) 1466-76. [DOI] [PubMed] [Google Scholar]
  • [21]. Butrynski J.E., D'Adamo D.R., Hornick J.L., Dal Cin P., Antonescu C.R., Jhanwar S.C., Ladanyi M., Capelletti M., Rodig S.J., Ramaiya N., Kwak E.L., Clark J.W., Wilner K.D., Christensen J.G., Janne P.A., Maki R.G., Demetri G.D., and Shapiro G.I., Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med 363 (2010) 1727-33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22]. Mano H., ALKoma: a cancer subtype with a shared target. Cancer Discov 2 (2012) 495-502. [DOI] [PubMed] [Google Scholar]
  • [23]. Fukuyoshi Y, Inoue H, Kita Y, Utsunomiya T, Ishida T, and Mori M, EML4-ALK fusion transcript is not found in gastrointestinal and breast cancers. Br J Cancer 98 (2008) 1536-1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [24]. Chon H.J., Kim H.R., Shin E., Kim C., Heo S.J., Lee C.K., Park J.K., Noh S.H., Chung H.C., and Rha S.Y., The Clinicopathologic Features and Prognostic Impact of ALK Positivity in Patients with Resected Gastric Cancer. Ann Surg Oncol 22 (2015) 3938-45. [DOI] [PubMed] [Google Scholar]
  • [25]. Alese O.B., El-Rayes B.F., Sica G., Zhang G., Alexis D., La Rosa F.G., Varella-Garcia M., Chen Z., Rossi M.R., Adsay N.V., Khuri F.R., and Owonikoko T.K., Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of the gastrointestinal tract. Ther Adv Med Oncol 7 (2015) 56-62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [26]. Mino-Kenudson M., Chirieac L.R., Law K., Hornick J.L., Lindeman N., Mark E.J., Cohen D.W., Johnson B.E., Janne P.A., Iafrate A.J., and Rodig S.J., A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry. Clin Cancer Res 16 (2010) 1561-71. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Cancer Biomarkers: Section A of Disease Markers are provided here courtesy of SAGE Publications

RESOURCES