Lauren classification combined with HER2 status is a better prognostic factor in Chinese gastric cancer patients

Miaozhen Qiu, Yixin Zhou, Xinke Zhang, Zixian Wang, Fang Wang, Jianyong Shao, Jiabin Lu, Ying Jin, Xiaoli Wei, Dongsheng Zhang, Fenghua Wang, Yuhong Li, Dajun Yang, Ruihua Xu, Miaozhen Qiu, Yixin Zhou, Xinke Zhang, Zixian Wang, Fang Wang, Jianyong Shao, Jiabin Lu, Ying Jin, Xiaoli Wei, Dongsheng Zhang, Fenghua Wang, Yuhong Li, Dajun Yang, Ruihua Xu

Abstract

Background: Lauren-classification and human epidermal growth factor receptor 2 (HER2) status are two important pathological features of gastric cancer patients. The prognostic value of HER2 in gastric cancer remains controversial. Intestinal type gastric cancer has better prognosis and higher HER2 positive proportion. What is the interaction between these two factors? We hypothesized that a combination of Lauren-classification and human epidermal growth factor receptor 2 (HER2) status (L-H status) might be more meaningful than either factor alone.

Methods: We collected 838 gastric cancer patients at all stages who had received treatment in our cancer center. This study was registered in the website of ClinicalTrials.Gov, with the number NCT01927146. We divided the patients into six groups according to their L-H status: Group A, HER2 negative and intestinal type; Group B, HER2 positive and intestinal type; Group C, HER2 negative and diffuse type; Group D, HER2 positive and diffuse type; Group E, HER2 negative and mixed type; and Group F, HER2 positive and mixed type.

Results: Diffuse type and intestinal type accounted for 51.0% and 33.9%, respectively. The proportion of HER2 positive patients was 11.2%, 25.4%, 2.1% and 10.2% in the whole patient group, intestinal, diffuse and mixed type, respectively. Median overall survival was 34.0 months, 25.3 months, 27.6 months, 19.2 months, 25.9 months and 26.4 months in the six groups patients, P = 0.053. There was a significant difference in survival among the first four groups (P < 0.001). HER2 was an independent prognostic factor in the intestinal type and in stage I + II patients, but not in the diffuse type or stage III + IV patients. L-H status was an independent prognostic factor in patients at all stages. For the diffuse and intestinal types, the multivariate analysis showed that HER2 was not an independent prognostic factor, while Lauren classification and L-H status were. Moreover, L-H status was a better prognostic factor than the Lauren classification.

Conclusions: L-H status is a prognostic factor in diffuse and intestinal type patients, but not in the mixed type. Patients with HER2 negative and intestinal type had the best survival, while patients with HER2 positive status and diffuse type had the worst survival.

Figures

Figure 1
Figure 1
The survival difference among different L-H status.
Figure 2
Figure 2
Kaplan–Meier curves of HER2-positive and -negative patients for overall survival in (A), intestinal type (B), diffuse type (C), TNM stage I/II and (D) TNM stage III/IV.
Figure 3
Figure 3
Kaplan–Meier curves of L-H status for overall survival in (A), TNM stage I/II and (B) TNM stage III/IV.

References

    1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137–2150. doi: 10.1200/JCO.2005.05.2308.
    1. Moore MA, Eser S, Igisinov N, Igisinov S, Mohagheghi MA, Mousavi-Jarrahi A, Ozenturk G, Soipova M, Tuncer M, Sobue T. Cancer epidemiology and control in North-Western and Central Asia - past, present and future. Asian Pac J Cancer Prev. 2010;11(Suppl 2):17–32.
    1. Hsu JT, Chen TC, Tseng JH, Chiu CT, Liu KH, Yeh CN, Hwang TL, Jan YY, Yeh TS. Impact of HER-2 overexpression/amplification on the prognosis of gastric cancer patients undergoing resection: a single-center study of 1,036 patients. Oncologist. 2011;16(12):1706–1713. doi: 10.1634/theoncologist.2011-0199.
    1. Sheng WQ, Huang D, Ying JM, Lu N, Wu HM, Liu YH, Liu JP, Bu H, Zhou XY, Du X. HER2 status in gastric cancers: a retrospective analysis from four Chinese representative clinical centers and assessment of its prognostic significance. Ann Oncol. 2013;24(9):2360–2364. doi: 10.1093/annonc/mdt232.
    1. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK, ToGA Trial Investigators 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):687–697. doi: 10.1016/S0140-6736(10)61121-X.
    1. Seshadri R, Horsfall DJ, Firgaira F, McCaul K, Setlur V, Chalmers AH, Yeo R, Ingram D, Dawkins H, Hahnel R. The relative prognostic significance of total cathepsin D and HER-2/neu oncogene amplification in breast cancer. The South Australian Breast Cancer Study Group. Int J Cancer. 1994;56(1):61–65. doi: 10.1002/ijc.2910560112.
    1. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–182. doi: 10.1126/science.3798106.
    1. Toikkanen S, Helin H, Isola J, Joensuu H. Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up. J Clin Oncol. 1992;10(7):1044–1048.
    1. Gomez-Martin C, Garralda E, Echarri MJ, Ballesteros A, Arcediano A, Rodriguez-Peralto JL, Hidalgo M, Lopez-Rios F. HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer. J Clin Pathol. 2012;65(8):751–757. doi: 10.1136/jclinpath-2012-200774.
    1. Jain S, Filipe MI, Gullick WJ, Linehan J, Morris RW. c-erbB-2 proto-oncogene expression and its relationship to survival in gastric carcinoma: an immunohistochemical study on archival material. Int J Cancer. 1991;48(5):668–671. doi: 10.1002/ijc.2910480506.
    1. Jorgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer - a systematic analysis of data from the literature. J Cancer. 2012;3:137–144. doi: 10.7150/jca.4090.
    1. He C, Bian XY, Ni XZ, Shen DP, Shen YY, Liu H, Shen ZY, Liu Q. Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer. World J Gastroenterol. 2013;19(14):2171–2178. doi: 10.3748/wjg.v19.i14.2171.
    1. Janjigian YY, Werner D, Pauligk C, Steinmetz K, Kelsen DP, Jager E, Altmannsberger HM, Robinson E, Tafe LJ, Tang LH, Shah MA, Al-Batran SE. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol. 2012;23(10):2656–2662. doi: 10.1093/annonc/mds104.
    1. Kataoka Y, Okabe H, Yoshizawa A, Minamiguchi S, Yoshimura K, Haga H, Sakai Y. HER2 expression and its clinicopathological features in resectable gastric cancer. Gastric Cancer. 2013;16(1):84–93. doi: 10.1007/s10120-012-0150-9.
    1. Qiu MZ, Li Q, Wang ZQ, Liu TS, Liu Q, Wei XL, Jin Y, Wang DS, Ren C, Bai L, Wei XL, Jin Y, Wang DS, Ren C, Bai L, Zhang DS, Wang FH, Li YH, Xu RH. HER2-positive patients receiving trastuzumab treatment have a comparable prognosis with HER2-negative advanced gastric cancer patients: a prospective cohort observation. Int J Cancer. 2014;134(10):2468–2477. doi: 10.1002/ijc.28559.
    1. Liang JW, Zhang JJ, Zhang T, Zheng ZC. Clinicopathological and prognostic significance of HER2 overexpression in gastric cancer: a meta-analysis of the literature. Tumour Biol. 2014;35(5):4849–4858. doi: 10.1007/s13277-014-1636-3.
    1. Lauren P. THE two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.
    1. Qiu MZ, Cai MY, Zhang DS, Wang ZQ, Wang DS, Li YH, Xu RH. Clinicopathological characteristics and prognostic analysis of Lauren classification in gastric adenocarcinoma in China. J Transl Med. 2013;11:58. doi: 10.1186/1479-5876-11-58.
    1. Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, Helin H, Salo J, Joensuu H, Sihvo E, Elenius K, Isola J. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16(2):273–278. doi: 10.1093/annonc/mdi064.
    1. Yamashita K, Sakuramoto S, Katada N, Futawatari N, Moriya H, Hirai K, Kikuchi S, Watanabe M. Diffuse type advanced gastric cancer showing dismal prognosis is characterized by deeper invasion and emerging peritoneal cancer cell: the latest comparative study to intestinal advanced gastric cancer. Hepato-Gastroenterology. 2009;56(89):276–281.
    1. Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Miwa S, Tsuneyama K, Takano Y. Pathobiological characteristics of intestinal and diffuse-type gastric carcinoma in Japan: an immunostaining study on the tissue microarray. J Clin Pathol. 2007;60(3):273–277. doi: 10.1136/jcp.2006.038778.
    1. Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375(9712):377–384. doi: 10.1016/S0140-6736(09)61964-4.
    1. Harrell FE, Jr, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA. 1982;247(18):2543–2546. doi: 10.1001/jama.1982.03320430047030.
    1. Kurokawa Y, Matsuura N, Kimura Y, Kawabata R, Adachi S, Fujita J, Nishikawa K, Takiguchi S, Mori M, Doki Osaka/JP Y. ESMO Abstr. 2012. Survival impact of HER2 status in patients with gastric cancer: a multicenter large-scale study in Japan; p. 677P.
Pre-publication history
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