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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 6  |  Issue : 2  |  Page : 203-207

Her2neu Expression of Gastric and Lower Esophageal Carcinoma and its Correlation with Clinicopathological Findings in Tertiary Care Hospital in Eastern India


1 Department of Pathology, Uttarpara SD Hospital, Uttarpara, West Bengal, India
2 Department of Pathology, Medical College, Kolkata, West Bengal, India
3 Department of Pathology, Rampurhat Government Medical College, Rampurhat, West Bengal, India
4 Department of Surgical Oncology, Medical College, Kolkata, West Bengal, India

Date of Submission08-Nov-2021
Date of Acceptance02-Jan-2022
Date of Web Publication17-Jun-2022

Correspondence Address:
Ayandip Nandi
48/7, Patuapara Lane, P.O.Serampore, Dt. Hooghly, Chinsurah - 712 201, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_295_21

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  Abstract 


Background: Gastric carcinomas are the fifth most common cancer worldwide and cause the second most common cancer-related deaths. Human epidermal growth factor receptor 2 (HER-2/Neu)(c-erbB2) protein overexpression in gastric cancer has been correlated to poor outcomes and a more aggressive disease. Targeted therapy against HER-2/Neu has attracted much attention recently. Comprehensive data regarding Her2neu expression in gastric carcinoma in Southeast Asia shows highly variable results and often lacks standardization. Aim/Objective: In this study, we study the expression of HER-2/Neu marker in lower esophageal and gastric carcinoma and compare it with various clinicopathological parameters and are known to have prognostic significance. Methods: One hundred and fifty cases of gastric/gastroesophageal adenocarcinomas (intestinal type) were included in the study over 2 years, and immunohistochemistry was done to evaluate Her2neu expression. Scoring was done according to the American Society of Clinical Oncology/College of American Pathologists guideline, and the finding was correlated with clinicopathological parameters. Results: The age of patients ranged from 41 years to 80 years. Gastric tumors were more common in the age group 61–70 years with mean age of 65.5 years. Gastric tumors are more common in males than females. (M:F = 3.16:1) Most common type of specimen received was partial gastrectomy (38%). Anorexia (46%) and pain abdomen (46%) were the most common presenting symptoms. Gastric tumors were common in tubular subtypes (76%) followed by mucinous subtypes (16%). Most common histopathological grading was moderately differentiated gastric adenocarcinoma (64%). Most gastric tumors were located at antropyloric area of the stomach (42%). The highest frequency of cases presented at an tumor, node, metastasis (TNM) stage that is pT2N2Mx (32.3%). Her2neu expression was found to be score 0 in most (62%) cases, only 10% of cancers were positive (3+), 14% were equivocal (2+), and another 14% were 1+ (negative). When we correlated clinicopathological parameters such as age,sex,tumour site,gross appearance,size,depth of invasion,TNM stage,Lymphovascular invasion,perineural invasion etc. with HEr2neu expression; no statistically significant correlation was found. Conclusion: Overexpression of HER-2/Neu in gastric carcinoma can help to identify patients with reduced survival and to identify eligible candidates for targeted therapy. A larger sample size and follow-up for a longer period might shed more light on the role of the above markers in gastric carcinoma.

Keywords: Gastric carcinoma, gastroesophageal junction adenocarcinoma, Her2neu, immunohistochemistry, prognosis


How to cite this article:
Chakraborty D, Ghosh S, Jain BB, Ghosh SK, Nandi A. Her2neu Expression of Gastric and Lower Esophageal Carcinoma and its Correlation with Clinicopathological Findings in Tertiary Care Hospital in Eastern India. Biomed Biotechnol Res J 2022;6:203-7

How to cite this URL:
Chakraborty D, Ghosh S, Jain BB, Ghosh SK, Nandi A. Her2neu Expression of Gastric and Lower Esophageal Carcinoma and its Correlation with Clinicopathological Findings in Tertiary Care Hospital in Eastern India. Biomed Biotechnol Res J [serial online] 2022 [cited 2022 Dec 9];6:203-7. Available from: https://www.bmbtrj.org/text.asp?2022/6/2/203/347714




  Intoduction Top


Gastric carcinomas are the fifth most common cancer worldwide and cause the second most common cancer-related deaths.[1],[2] More than 50% of cases present in advanced unresectable stages making cure impossible. The morphological and histological types of gastric carcinomas are variable and they do not correlate well with the prognosis. HER-2/Neu (c-erbB2) has been proposed as potential tool for the evaluation of the prognosis of gastric cancer. HER-2/Neu overexpression in gastric cancer has been correlated to poor outcomes and a more aggressive disease.[3] About 8%–22% worldwide gastric carcinoma patients and about 24% of lower gastroesophageal junction express HER-2/Neu.[4],[5] Targeted therapy against HER-2/Neu has attracted much attention recently. Comprehensive data regarding Her2neu expression in gastric carcinoma in Southeast Asia are lacking and need larger sample study.

Objective

In this study, we study the expression of HER-2/Neu marker in lower esophageal and gastric carcinoma and compare it with various clinicopathological parameters and are known to have prognostic significance.


  Material and Methods Top


This institution-based observational cross-sectional study design began after obtaining permission from institutional ethical committee with collaboration from department of surgical oncology and pathology till the period from January 2017 to June 2018 (Ref No MC/Kol/IEC/Non-spon/446/11/2016 Dated 10 Dec 2016). All patients diagnosed as adenocarcinoma (intestinal type) from resection specimens as well as mucosal biopsies of stomach and lower esophagus were included in our study. Any malignancies other than intestinal adenocarcinoma were excluded.

Sample size was calculated using Epi Info software as 140 (prevalence of gastric carcinoma in population ⁓10%,[6] with 5% margin of error and 95% confidence interval). Patient's relevant clinical history, endoscopic findings, biochemical, and hematological parameters were evaluated from records. After obtaining informed consent from patient party, routine histological examination was done from endoscopic/resection specimens, and immunohistochemical (IHC) analysis for Her-2-neu was done along with known positive and negative control in each run. IHC was done using TRIS buffer-based moist antigen retrieval using pressure cooker in alkaline pH (8.6) by polymer detection kit. Primary antibody used for Her2 was by BioGenex for antihuman c-erbB-2[SP101] IMMUNOGEN: a recombinant protein encoding extracellular domain of human c-erbB-2; CLONE: SP101; SPECIES: Rabbit; immunoglobulin G (ready to use).

Results were analyzed and scored as such (American Society of Clinical Oncology/College of American Pathologists guideline)[6] [Figure 1].
Figure 1: Human epidermal growth factor receptor 2-neu expression in gastric cancer (×40, human epidermal growth factor receptor 2-neu) depicting scores 0, 1+, 2+, 3+

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0/negative: No staining is observed or basolateral membrane staining in <10% of tumor cells.

1+/negative: A faint barely perceptible basolateral membrane staining detected. Greater than 10% of tumor cells.

2+/borderline: A weak-to-moderate complete basolateral membrane staining is observed in >10% of tumor cells.

3+/positive: A strong complete basolateral membrane staining is observed in >10% of tumor cells.

Results were tabulated and analyzed with software Epi Info, version 7.2.2.6 developed by Centers for disease control and prevention,Atlanta,Georgia.


  Results and Analysis Top


A total number of 150 cases of gastric and lower esophageal adenocarcinoma were studied. The age of patients ranged from 41 years to 80 years. Gastric tumors were more common in the age group 61–70 years (48%), with mean age of 65.5 years. Gastric tumors are more common in males than females. (M: F = 3.16:1). Most common type of specimen received was partial gastrectomy (38%). Anorexia (46%) and pain abdomen (46%) were the most common presenting symptoms followed by dyspepsia (42%). Gastric tumors were common in tubular subtypes (76%) followed by mucinous subtypes (16%). Most common histopathological grading was moderately differentiated gastric adenocarcinoma (64%). Forty-two percent had gastric tumors located at antropyloric area of the stomach. Most common gross presentation was an ulceroproliferative growth in about 46%. Maximum number of cases of gastric tumor was of blood Group “A” (40%) followed by blood Group O (16%). Seventy percent of patients were smokers and 54% had history of alcohol intake. The highest frequency of cases presented at an tumor, node, and metastasis (TNM) stage that is PT2N2Mx (32.3%). The Her2neu expression is summarized in [Table 1].
Table 1: Human epidermal growth factor receptor 2 expression patterns in gastric and lower esophageal tumors

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When we correlated clinicopathological parameters such as age,sex,tumour site,gross appearance,size,depth of invasion,TNM stage,Lymphovascular invasion,perineural invasion etc. with HEr2neu expression; no statistically significant correlation was found. [Table 2].
Table 2: Association of clinicopathological parameters along with human epidermal growth factor receptor 2 expression

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  Discussion Top


Many biological markers are being studied in several parts of the world to identify their possible role in the evaluation of gastric carcinoma and thus in clinical outcomes. HER-2/Neu has been proposed to have prognostic value.

In this study, IHC evaluation was done in 150 gastric carcinoma cases; attempt was made to correlate the expression with HER-2/Neu with various clinicopathological factors and known prognostic factors of gastric carcinoma.

There is a male preponderance of gastric carcinoma throughout the world.[7] In the current study, the incidence of gastric carcinoma in males and females was 76% and 24%, respectively, same as other studies done in Southeast Asian countries.[8],[9]

In study of age cohort, the age of the patients ranged from 41 years to 80 years, gastric carcinoma was found more in the age group 61–70 with a mean age of 60.5 years. In the western world, the mean age was 71 years in USA and 61 years in Japan.[10],[11]

The prevalence of gastric neoplasm is closely linked to socioeconomic factors such as low income, poor education, and living conditions during childhood such as poor sanitation and overcrowding.[12] In our study, we found anorexia (46%) and pain abdomen (46%) to be the most common presenting symptom followed by dyspepsia (42%). In a study by Kabir et al., abdominal pain, vomiting, dysphagia, and weight loss were predominant symptoms pertaining to gastric carcinoma.[12] Qurieshi et al. also showed common presenting symptoms as weight loss (35%), dyspepsia (76%), anorexia (35%), and vomiting (35.8%).[13]

Our study found blood Group A (40%) was more prevalent among gastric carcinoma followed by blood group by O (24%). In one of the studies done by Aird et al. were the first to notice correlation of gastric cancer and blood Group A. Risk is increased in blood Group A.[14] The most common site of gastric carcinoma in this study was antropyloric (42%) which is similar to the study of Fondevila et al. showing the occurrence of 51% cases of pyloroantrum.[15]

Various reports reveal progressive increase in proximal stomach cancer in Asian countries and concomitant decline in distal stomach cancer in the western world. Qurieshi et al. showed that in Kashmiri population incidence of cancer in proximal, mid, and distal stomach were 42%, 6.2%, and 45.7, respectively.[13]

Among the various histological types, tubular carcinoma was the most common type accounting for (76%) of cases in the study which is almost similar to that observed by Kakeji et al. in their study.[16]

In this study, moderately differentiated grade tumor was more common than other grades accounting for (64%)% of cases which is similar to observations made by Fondevila et al. (47%).[15] In this study, a higher proportion of tumor being to T2 subtype (79.5%) whereas most other studies found highest no. of cases presented at an advanced stage.[17]

Among the resected specimens, 80% had lymphovascular invasion. This is similar to the observations obtained by Choi et al., showing lymphatic invasion in 79.35% of cases.[17] In this study, 20% of cases showed perineural infiltration this was almost similar to the results obtained by Tianhang et al., showing 31.7% of cases with perineural invasion.[18]

Comparison of expression of the abovementioned marker with other literature shows her-2/neu ranging from 5% to 26%.[19],[20],[21],[22],[23] [Table 3] These fluctuations could be due to different methodologists used for evaluation and to varying characteristics of the studied case. Our study shows 24%.
Table 3: Comparison of human epidermal growth factor receptor 2 expression with world statistics

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Raziee et al. studied 100 cases of gastric carcinoma in Iran and found a significant association of HER-2/Neu overexpression with Lauren's intestinal type of tumor and well-differentiated grade, and no association between age, gender, location of tumor, and depth of infiltration.[19]

Moleans et al. found Her2neu overexpression was more frequent in gastroesophageal junction cancers than gastric cancers.[20] Ballestín et al. studied 181 cases in Spain and they found HER2/neu overexpression/amplification in 13.5%. There was no significant correlation of HER2/neu overexpression/amplification with both tumor localization and histological subtype.[21]

Xie et al. studied 218 cases and they were able to demonstrate a statistically significant association of HER-2/Neu overexpression with survival of the patient and were not able to demonstrate association with any other known clinicopathological and prognostic factors.[22]

Vergara et al. studied 90 cases of gastric carcinoma and found a statistically significant association of HER-2/Neu overexpression with depth of infiltration and no association with grade, histological subtype, or survival.[23] Zhang et al. studied 102 cases of gastric cancer in Korea and found a significant association between HER-2/Neu overexpression and Lauren's type and depth of infiltration and no association with grade, histological type, or survival.[24]

Although in our study, only the score 3+ is taken as positive, but like in breast cancer, 2+ score should be taken as equivocal result and needs to be confirmed further by FISH, to check gene overexpression. To see whether the same is applicable for HER-2/Neu expression in cases of gastric carcinoma also or not needs to be confirmed by investigation like FISH which was beyond the scope of our present work. Larger sample followed for longer time is required for survival studies, which we could not do.


  Conclusion Top


In our study, increased frequency of HER-2/Neu overexpressed cases was belonged to tubular type, moderately differentiated grade, and T2 level of infiltration, with stage II being the most common, male preponderance, gross was mainly ulceroproliferative, but statistically significant association could not be ascertained. To conclude, identifying the expression of HER-2/Neu in gastric carcinoma can help to identify patients with reduced survival and to identify eligible candidates for targeted therapy.

A larger sample size and follow-up for a longer period might shed more light on the role of the above markers in gastric carcinoma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43-66.  Back to cited text no. 1
    
2.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.  Back to cited text no. 2
    
3.
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;24:2137-50.  Back to cited text no. 3
    
4.
Meza-Junco J, Au HJ, Sawyer MB. Critical appraisal of trastuzumab in treatment of advanced stomach cancer. Cancer Manag Res 2011;3:57-64.  Back to cited text no. 4
    
5.
Kataoka Y, Okabe H, Yoshizawa A, Minamiguchi S, Yoshimura K, Haga H, et al. HER2 expression and its clinicopathological features in resectable gastric cancer. Gastric Cancer 2013;16:84-93.  Back to cited text no. 5
    
6.
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 2013;31:3997-4013.  Back to cited text no. 6
    
7.
Griffith GW. The sex ratio in gastric cancer and hypothetical considerations relative to aetiology. Br J Cancer 1968;22:163-72.  Back to cited text no. 7
    
8.
Phukan RK, Zomawia E, Narain K, Hazarika NC, Mahanta J. Tobacco use and stomach cancer in Mizoram, India. Cancer Epidemiol Biomarkers Prev 2005;14:1892-6.  Back to cited text no. 8
    
9.
Afridi SP, Bano F, Rahman SU. Pattern and presentation of carcinoma stomach. J Coll Physicians Surg Pak 2011;21:161-3.  Back to cited text no. 9
    
10.
Julian AA, Timothy CW. Adenocarcinoma and other tumours of the stomach. In: Feldman LS, Brandt LJ, editors. Sleisenger and Fordtrean's Gastrointestinal and Liver disease. 9th ed. Philadelphia, Pa, USA: Elsevier Saunders; 2010.  Back to cited text no. 10
    
11.
Kurosawa M, Kikuchi S, Inaba Y, Ishibashi T, Kobayashi F. Helicobacter pylori infection among Japanese children. J Gastroenterol Hepatol 2000;15:1382-5.  Back to cited text no. 11
    
12.
Kabir M, Barua R, Masud H, Ahmed D, Islam M, Karim E, et al. Clinical presentation, histological findings and prevalence of helicobacter pylori in patients of gastric carcinoma. Faridpur Med Coll J 2011;6:78-81. [doi: 10.3329/fmcj.v6i2.9205].  Back to cited text no. 12
    
13.
Qurieshi MA, Masoodi MA, Kadla SA, Ahmad SZ, Gangadharan P. Gastric cancer in kashmir. Asian Pac J Cancer Prev 2011;12:303-7.  Back to cited text no. 13
    
14.
Aird I, Bentall HH, Roberts JA. A relationship between cancer of stomach and the ABO blood groups. Br Med J 1953;1:799-801.  Back to cited text no. 14
    
15.
Fondevila C, Metges JP, Fuster J, Grau JJ, Palacín A, Castells A, et al. p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer 2004;90:206-15.  Back to cited text no. 15
    
16.
Kakeji Y, Korenaga D, Tsujitani S, Baba H, Anai H, Maehara Y, et al. Gastric cancer with p53 overexpression has high potential for metastasising to lymph nodes. Br J Cancer 1993;67:589-93.  Back to cited text no. 16
    
17.
Choi JY, Ha TK, Kwon SJ. Clinicopathologic characteristics of gastric cancer patients according to the timing of the recurrence after curative surgery. J Gastric Cancer 2011;11:46-54.  Back to cited text no. 17
    
18.
Tianhang L, Guoen F, Jianwei B, Liye M. The effect of perineural invasion on overall survival in patients with gastric carcinoma. J Gastrointest Surg 2008;12:1263-7.  Back to cited text no. 18
    
19.
Raziee HR, Taghizadeh A, Ghaffarzadegan K, Shakeri MT, Ghavamnasiri M. HER2/neu expression in resectable gastric cancer and its relationship with histopathologic subtype, grade, and stage. Iran J Basic Med Sci 2007;10:139-45.  Back to cited text no. 19
    
20.
Moelans CB, van Diest PJ, Milne AN, Offerhaus GJ. Her-2/neu testing and therapy in gastroesophageal adenocarcinoma. Patholog Res Int 2010;2011:674182.  Back to cited text no. 20
    
21.
Ballestín C, López-Rios F, Vicioso L, Burgos F, Adrados M, Nieto S, et al. HER2/neu overexpression/amplification in Advanced Gastric Cancer (AGC) Patients (pts): Correlation with clinicopathological parameters. J Clin Oncol 2007;25:15046.  Back to cited text no. 21
    
22.
Xie SD, Xu CY, Shen JG, Jiang ZN, Shen JY, Wang LB. HER 2/neu protein expression in gastric cancer is associated with poor survival. Mol Med Rep 2009;2:943-6.  Back to cited text no. 22
    
23.
Vergara R, Torrazza I, Fernandez OC. HER-2/Neu overepression in gastric cancer. J Clin Oncol 2009;27 Suppl 15:e15679-924.  Back to cited text no. 23
    
24.
Zhang XL, Yang YS, Xu DP, Qu JH, Guo MZ, Gong Y, et al. Comparative study on overexpression of HER2/neu and HER3 in gastric cancer. World J Surg 2009;33:2112-8.  Back to cited text no. 24
    


    Figures

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    Tables

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Intoduction
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