The Prognostic Significance of c-Met and p53 Immunohistochemical Expression in Gastric and Colorectal Carcinomas

Amany A. Abou-Bakr; Alshaymaa A.  Abdelaziz; Ibrahim A.  Malash; Osman Mansour; Ibrahim M. Abdelsalam; Omnia M. Abo-Elazm; Heba A. Ibrahim; Mai S. Mohammed; Rasha Khairy

doi:10.3889/oamjms.2021.5910

Authors

Amany A. Abou-Bakr Department of Pathology, National Cancer Institute, Cairo University, Cairo, Egypt
Alshaymaa A. Abdelaziz Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
Ibrahim A. Malash Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
Osman Mansour Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
Ibrahim M. Abdelsalam Department of Tumor Biology, National Cancer Institute, Cairo University, Cairo, Egypt https://orcid.org/0000-0001-5559-7981
Omnia M. Abo-Elazm Department of Biostatistics and Cancer Epidemiology, National Cancer Institute, Cairo University, Cairo, Egypt
Heba A. Ibrahim Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
Mai S. Mohammed Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
Rasha Khairy Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt https://orcid.org/0000-0002-9373-354X

DOI:

https://doi.org/10.3889/oamjms.2021.5910

Keywords:

Gastric, Cancer, Colorectal carcinoma, TP53, c-Met

Abstract

BACKGROUND: Colorectal and gastric carcinomas are the most common and deadly gastrointestinal (GIT) malignancies.

AIM: This study aimed to evaluate the expression of c-Met and p53 in gastric and colorectal carcinomas (CRCs) as well as colorectal adenomas using immunohistochemistry.

MATERIALS AND METHODS: c-Met and p53 immunohistochemical expression was conducted on 66 cases of gastric adenocarcinomas and total of 60 colonic cases (36 CRCs and 24 colorectal adenomas).

RESULTS: In this study, c-Met was positively expressed in 54.5% of gastric carcinomas and 50% of CRCs. In addition, p53 was positively expressed in 56.1% of gastric carcinomas and 72.2% of CRCs. Moreover, higher expression of both c-Met (p = 0.001) and p53 expression (p < 0.001) was reported in CRCs compared to colorectal adenomas. In the same context, c-Met and p53 expressions were positively correlated with intestinal type gastric adenocarcinoma (p < 0.001 and p = 0.03, respectively). Moreover, c-Met was correlated with non-mucinous adenocarcinomas (p = 0.008) and lower grades (p < 0.001) of gastric carcinomas. As regard survival analysis in gastric carcinomas, median overall survival (OS) was better in p53 positive patients (p = 0.05), patients with negative lymph node metastasis (p = 0.03), and patients with better response to neoadjuvant chemotherapy (p = 0.04). In contrast, c-Met did not exhibit significant correlation with OS (p > 0.05). Both c-Met and p53 did not reveal significant correlation with tumor stage and site in both CRCs and gastric carcinomas (p > 0.05).

CONCLUSION: We concluded that c-Met and p53 are expressed in the most common GIT malignancies addressing them as potential biomarkers. In addition, c- Met and p53 may have a potential role in colorectal cancer development as they showed higher positivity in CRCs compared to adenomas.

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References

Sisik A, Kaya M, Bas G, Basak F, Alimoglu O. CEA and CA 19-9 are still valuable markers for the prognosis of colorectal and gastric cancer patients. Asian Pac J Cancer Prev. 2013;14(7):4289-94. https://doi.org/10.7314/apjcp.2013.14.7.4289 PMid:23991991 DOI: https://doi.org/10.7314/APJCP.2013.14.7.4289

Gayyed M, El-Maqsoud N, El-Heeny A, Mohammed M. c-MET expression in colorectal adenomas and primary carcinomas with its corresponding metastases. J Gastrointest Oncol. 2015;6(6):618-27.PMid: 26697193

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. https://doi.org/10.3322/caac.21492 PMid:30207593 DOI: https://doi.org/10.3322/caac.21492

Ibrahim A, Khaled H, Mikhail N, Baraka H, Kamel H. Cancer incidence in Egypt: Results of the national population-based cancer registry program. J Cancer Epidemiol. 2014;2014:437971. https://doi.org/10.1155/2014/437971 PMid:25328522 DOI: https://doi.org/10.1155/2014/437971

Jia Y, Dai G, Wang J, Gao X, Zhao Z, Duan Z, et al. c-MET inhibition enhances the response of the colorectal cancer cells to irradiation in vitro and in vivo. Oncol Lett. 2016;11(4):2879-85. https://doi.org/10.3892/ol.2016.4303 PMid:27073569 DOI: https://doi.org/10.3892/ol.2016.4303

Bradley CA, Salto-Tellez M, Laurent-Puig P, Bardelli A, Rolfo C, Tabernero J, et al. Review targeting c-MET in gastrointestinal tumours: Rationale, opportunities and challenges. Nat Rev Clin Oncol. 2017;14(9):562-76. https://doi.org/10.1038/nrclinonc.2017.40 PMid:28374784 DOI: https://doi.org/10.1038/nrclinonc.2017.40

Huang TJ, Wang JY, Lin SR, Lian ST, Hsie JS. Overexpression of the c-met protooncogene in human gastric carcinoma. Acta Oncol. 2001;40(5):638-43. PMid:11669338 DOI: https://doi.org/10.1080/028418601750444204

Kumar V, Abbas AK. Fausto N, Aster AC. Pathologic Basis of Diseases. 8th ed. Philadelphia, PA: Saunders; 2004. p. 302-3.

Levine AJ, Finlay CA, Hinds PW. p53 is a tumor suppressor gene. Cell. 2004;S116:S67-9. https://doi.org/10.1016/s0092-8674(04)00036-4 DOI: https://doi.org/10.1016/S0092-8674(04)00036-4

Petitjean A, Achatz MI, Borresen-Dale AL, Hainaut P, Olivier M. TP53 mutations in human cancers: Functional selection and impact on cancer prognosis and outcomes. Oncogene. 2007;26(15):2157-65. https://doi.org/10.1038/sj.onc.1210302 PMid:17401424 DOI: https://doi.org/10.1038/sj.onc.1210302

Eisenhauera EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline; (version 1.1). Eur J Cancer. 2009;45(2):228-47. https://doi.org/10.1016/j.ejca.2008.10.026 PMid:19097774 DOI: https://doi.org/10.1016/j.ejca.2008.10.026

Hamilton SR, Bosman FT, Boffetta P, Ilyas M, Morreau H, Nakamura S. Carcinoma of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO Classification of Tumours of the Digestive System. 4th ed. Lyon: IARC Press; 2010. p. 134-46.

Edge SB, Byrd DR, Compton CC, Fritz AG, Greene F, Trotti A. AJCC Cancer Staging Handbook. 7th ed. New York: Springer; 2010. p. 473-206.

Fleming M, Ravula S, Tatishchev S, Wang H. Colorectal carcinoma: Pathologic aspects. J Gastrointest Oncol. 2012;3(3):153. PMid:22943008

Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89-103. https://doi.org/10.5114/pg.2018.81072 PMid:31616522 DOI: https://doi.org/10.5114/pg.2018.81072

Chen CY, Wu CW, Lo SS, Hsieh MC, Lui WY, Shen KH. Peritoneal carcinomatosis and lymph node metastasis are prognostic indicators in patients with Borrmann type IV gastric carcinoma. J Hepatogastroenterol. 2002;49(45):387. PMid:12064011

Heitman SJ, Ronksley PE, Hilsden RJ, Manns BJ, Rostom A, Hemmelgarn BR, et al. Prevalence of adenomas and colorectal cancer in average risk individuals: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2009;7(12):1272-8. https://doi.org/10.1016/j.cgh.2009.05.032 PMid:19523536 DOI: https://doi.org/10.1016/j.cgh.2009.05.032

Druliner BR, Wang P, Bae T, Baheti S, Slettedahl S, Mahoney D, et al. Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations. Sci Rep. 2018;8(1):3161. https://doi.org/10.1038/s41598-018-21525-4 PMid:29453410 DOI: https://doi.org/10.1038/s41598-018-21525-4

Saigusa S, Toiyama Y, Tanaka K, Yokoe T, Fujikawa H, Matsushita K, et al. Inhibition of HGF/cMET expression prevents distant recurrence of rectal cancer after preoperative chemoradiotherapy. Int J Oncol. 2012;40(2):583-91. https://doi.org/10.3892/ijo.2011.1200 PMid:21922134 DOI: https://doi.org/10.3892/ijo.2011.1200

Abou-Bakr A, Elbasmi A. c-MET overexpression as a prognostic biomarker in colorectal adenocarcinoma. Gulf J Oncolog. 2013;1(14):28-34. PMid:23996864

Guo T, Yang J, Yao J, Zhang Y, Da M, Duan Y. Expression of MACC1 and c-Met in human gastric cancer and its clinical significance. Cancer Cell Int. 2013;13(1):121. https://doi.org/10.1186/1475-2867-13-121 PMid:24325214 DOI: https://doi.org/10.1186/1475-2867-13-121

Stuebs P, Dittmar F, Zierau K, Fahlke J, Ridwelski K, Kristin A, et al. The characteristics of c-MET and HER2 expression in gastric carcinoma and its correlation with clinical-pathological parameters. J Clin Oncol. 2017;35(15):e15566. https://doi.org/10.1200/jco.2017.35.15_suppl.e15566 DOI: https://doi.org/10.1200/JCO.2017.35.15_suppl.e15566

Lee HE, Kim MA, Lee HS, Jung EJ, Yang HK, Lee BL, et al. c-MET in gastric carcinomas: Comparison between protein expression and gene copy number and impact on clinical outcome. Br J Cancer. 2012;107:325-33. https://doi.org/10.1038/bjc.2012.237 PMid:22644302 DOI: https://doi.org/10.1038/bjc.2012.237

Sotoudeh K, Hashemi F, Madjd Z, Sadeghipour A, Molanaei S, Kalantary E. The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays. Diagn Pathol. 2012;7:57. https://doi.org/10.1186/1746-1596-7-57 PMid:22640970 DOI: https://doi.org/10.1186/1746-1596-7-57

Banu L, Sülen S, Selman S, Ellidokuz H, Füzün M, Küpelioğlu A. The clinical significance of P53, P21,and P27 expressions in rectal carcinomas. Appl Immunohistochem Mol Morphol. 2005;13(1):38-44. PMid:15722792 DOI: https://doi.org/10.1097/00129039-200503000-00007

Mcgregor MJ, Fadhil W, Wharton R, Yanagisawa Y, Presz M, Pritchard A, et al. Aberrant P53 expression lacks prognostic or predictive significance in colorectal cancer: Results from the VICTOR trial. Anticancer Res. 2015;35(3):1641-5. PMid:25750322

Starzynska T, Bromley M, Ghosh A, Stern PL. Prognostic significance of p53 overexpression in gastric and colorectal carcinoma. Br J Cancer. 1992;66(3):558-62. https://doi. org/10.1038/bjc.1992.314 PMid:1520594 DOI: https://doi.org/10.1038/bjc.1992.314

Vernillo R, Lorenzi B, Banduccci T, Minacci C, Vindigni C, Fei AL, et al. Immunohistochemical expression of p53 and ki67 in colorectal adenomas and prediction of malignancy and development of new polyps. Int J Biol Markers. 2008;23(2):89- 95. https://doi.org/10.1177/172460080802300205 PMid:18629781 DOI: https://doi.org/10.1177/172460080802300205

Sousa WA, Rodrigues LV, Silva RG Jr., Vieira FL. Immunohistochemical evaluation of p53 and Ki-67 proteins in colorectal adenomas. Arq. Gastroenterol. 2012;49(1):35-40. https://doi.org/10.1590/s0004-28032012000100007 PMid:22481684 DOI: https://doi.org/10.1590/S0004-28032012000100007

American Cancer Society. Cancer Facts and Figures. Atlanta, GA: American Cancer Society; 2019. Available from: http:// www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/ cancer-facts-and-figures-2019.

Shiraishi N, Sato K, Yasuda K, Inomata M, Kitano A. Multivariate prognostic study on large gastric cancer. J Surg Oncol. 2007;96(1):14-8. https://doi.org/10.1002/jso.20631 PMid:17582596 DOI: https://doi.org/10.1002/jso.20631

Achilli P, Martini PD, Ceresoli M, Mari GM, Costanzi A, Maggioni D, et al. Tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma: A prospective, multi-center cohort study. J Gastrointest Oncol. 2017;8(6):1018-25. https://doi.org/10.21037/jgo.2017.08.13 PMid:29299362 DOI: https://doi.org/10.21037/jgo.2017.08.13

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. 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. 2010;376(9742):687-97. https://doi.org/10.1016/ s0140-6736(10)61121-x PMid:20728210

Yildirim M, Kaya V, Demirpence O, Gunduz S, Bozcuk H. Prognostic significance of p53 in gastric cancer: A meta-analysis. Asian Pac J Cancer Prev. 2015;16(1):327-32. https://doi.org/10.7314/apjcp.2015.16.1.327 PMid:25640374 DOI: https://doi.org/10.7314/APJCP.2015.16.1.327

Retterspitz MF, Mönig SP, Schreckenberg S, Schneider PM, Hölscher AH, Dienes HP, et al. Expression of {beta}- catenin, MUC1 and c-met in diffuse-type gastric carcinomas: Correlations with tumour progression and prognosis. Anticancer Res. 2010;30(11):4635-41. PMid:21115917