Human Epidermal Growth Factor Receptor-2 in Sri Lankan Gastric Carcinoma Patients with Clinicopathological Association and Survival

Subasinghe, Duminda; Sivaganesh, Sivasuriya; Samarsekera, Ananthi; Kumarasinghe, M. Priyanthi; Samarasekera, Dharmabandhu Nandadeva; Lokuhetty, M. D. S.

doi:10.1007/s10620-017-4647-2

Cited by 6 publications

(12 citation statements)

References 48 publications

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“…In addition, the positive rate of HER2 protein is 31.3% higher in gastric cancer patients with negative vascular invasion (25/80) and the result has obvious statistical signi cance (p=0.036). Some studies have reported ndings similar to those of this study regarding the anatomical location of the tumor, indicating that there is no difference between distal and proximal GC tumors 2,11,23 . The e cacy of trastuzumab in breast cancer therapy has led to emerging interest in its therapeutic effect in patients with HER2 protein positive GC.…”

Section: Discussionsupporting

confidence: 84%

“…Patients: This retrospective study involved in a cohort of 176 GC patients who underwent curative surgery for primary GC at The Second A liated Hospital, College of Medicine, Zhejiang University, between January 2014 and December 2016. Patients enrolled in the study met the following criteria: (1) patients were pathologically diagnosed as GC after gastrectomy by two experienced physicians; (2) The clinicopathological data were obtained from the hospital information system (Electronic Medical Record System, EMRS).…”

Section: Methodsmentioning

confidence: 99%

“…Gastric cancer (GC) is the third leading cause of cancer-related death worldwide after lung and liver cancer 1 . Although the incidence of GC has decreased worldwide, more than half of the cases occur in Eastern Asia, leading to a signi cant public health problem in those countries, including China 1,2 . Despite advanced methods of early detection and the multidisciplinary treatment of advanced GC, the 5-year survival still remains unsatisfactory, although better results are achieved in Japan and South Korea 3 .…”

Section: Introductionmentioning

confidence: 99%

“…Also, in such studies the HER2 protein expression status was measured by immunohistochemistry (IHC) and the (normal, deletion or ampli cation) status was evaluated by uorescence in situ hybridization (FISH) analysis; those patients with IHC 3+ or IHC grade 2+ and FISH+ were considered HER2 protein overexpression. Recently, several studies reported the clinical characteristics and prognosis relating with HER2 protein overexpression in GCs 2,13,14 . However, the conclusions drawn from such studies were varied.…”

Section: Introductionmentioning

confidence: 99%

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HER2 protein expression correlates with Lauren classification and P53 in gastric cancer patients

Chu

et al. 2020

Preprint

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Background and objective: Human epidermal growth factor receptor 2 (HER2) is a key pathological characteristic in gastric cancer patients. However, the clinical significance of HER2 protein expression in gastric carcinoma remains controversial. The purpose of the study is to analyze the clinicopathological characteristics of HER2 protein expression, Lauren classification and P53 expression and evaluate the clinical significance of the HER2 protein expression. Methods: A total of 176 consecutive patients were recruited prospectively between January 2014 and December 2016 in The Second Affiliated hospital of Zhejiang University School of Medicine. Histological analysis was performed on resected tissue for HER2 protein expression by immunohistochemistry (IHC). The patients with IHC grade 2+ were analyzed by fluorescence in situ hybridization (FISH) to assess the expression status of HER2 protein. Moreover, standardized criteria of HER2 protein expression in gastric cancer was used in this study. Additionally, the expression status of HER2 protein and clinicopathological features were analyzed by Chi-square (c2) test. All statistical analyses were conducted using the SPSS 22.0 statistical software program (IBM Corp., SPSS statistics, Chicago, IL).Results: A total of 176 gastric cancer patients were enrolled in this study. Intratumorally heterogeneity of HER2 protein overexpression was 42 of 176 cases with IHC grade 2+ accompanied with FISH positivity and IHC grade 3+. HER2 protein expression correlated with tumor differentiation (p < 0.001), Lauren classification (p = 0.001), Borrmann type (p = 0.003) and P53 expression (p < 0.001). Overall survival (OS) was not analyzed because the follow-up duration was too short and the high rate of missed interview.Conclusions: The overexpression of HER2 protein was determined in 23.9% of the cases and significantly related to Lauren intestinal subtype and P53 expression.

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Section: Discussionsupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HER2 protein expression correlates with Lauren classification and P53 in gastric cancer patients

Chu

et al. 2020

Preprint

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“…The reported frequency of HER2 protein overexpression by immunohistochemistry (IHC) in GC ranges from 8.2% to 40.3% [1][2][3][4][5][6][9][10][11][12] . Only a single documentation is available from Sri Lanka of HER2 expression by IHC in Sri Lankan GC patients.…”

Section: Introductionmentioning

confidence: 99%

Human Epidermal Growth Factor Receptor-2(HER-2) expression in Sri Lankan gastric adenocarcinoma patients: An analysis of the concordance of HER2 expression and survival based on silver in-situ hybridization (SISH)

Subasinghe

Acott

Mahesh

et al. 2021

Preprint

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Background: Accurate HER2 status is crucial for gastric adenocarcinoma (GC) patient selection for antiHER2 therapy. It is assessed immunohistochemically (IHC) for protein expression, and by silver in-situ hybridization (SISH) for gene copy number. This study aimed to evaluate the concordance of HER2 status by IHC/SISH analyses and HER2-SISH based survival.Methods: This prospective study includes 145 GC’s (excluding gastro-oesophageal-junction tumours) from the National Hospital of Sri Lanka with defined demographic, clinical-radiological-pathological characteristics. HER2-IHC was assessed by DAKO A0485, RealTM Envision system and interpreted using Ruschoff criteria. HER2-SISH was assessed with INFORM HER2 dual ISH DNA Probe Cocktail. Concordance between HER2 IHC/SISH results was determined by Cohens kappa statistics. The association between the survival and HER2-SISH positivity was evaluated using the cox-regression method. Adjustments were done for age, gender, Lauren classification, tumour location and the tumour staging.Results: Of the 69 gastrectomies and 76 biopsies, 8.3% (n = 12) were HER2-IHC positive (n = 7, + 2 and n = 5, + 3). HER2-SISH positivity was 4.8 % (n = 7). All IHC + 3 were SISH positive, while two + 2 cases were SISH positive. Concordance for IHC 0, + 1, +3 were 100%. There was a significant overall correlation (kappa = 0.72, p < 0.001) between HER2-IHC and HER2-SISH indicating substantial concordance. The mean overall survival of HER2-SISH negative and positive patients were 41.7 (0-210) and 14.6 (3–51) weeks respectively, after a mean duration of patient follow up for 40.4 weeks (range 0-210). Survival was relatively lower (p = 0.001) in the group with HER2-SISH positivity.Conclusion: HER2-IHC was well concordant with HER2-SISH for 0, + 1, +3 scores and could be used for treatment and prognostication in low resource settings, where SISH facility is unavailable. HER2-IHC + 2, without gene amplification may be due to transcriptional activation by other genes or post-transcriptional events, mandating further evaluation by SISH. Survival of GC patients is significantly affected by HER2-SISH positive status.

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Delay in diagnosis to treatment and impact on survival of gastric adenocarcinoma in a low income setting without screening facility

Subasinghe,

Mahesh,

Wijesinghe

et al. 2023

Sci Rep

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The treatment modality of gastric adenocarcinoma (GCA) depends on the stage of the disease at the clinical presentation. Long delays are probably an unfavorable factor for the patient's prognosis. A prospective longitudinal, study involving 145 consecutive GCA was conducted at the National Hospital of Sri Lanka (NHSL). The overall delay (in weeks) was recorded for each patient and divided into four periods-patient, endoscopy, pathology and treatment. The median and Interquartile Range (IQR) duration of delays were calculated and differences were explored with chi square test and Mann Whitney U test Survival analysis was done with Kaplan Meier technique and Cox regression. The median duration of delays for patient, endoscopy, histology reporting delay, other histology delay (specimen transfer delay and report receipt delay) and treatment were 18 (IQR 14–27), 2 (IQR 2–3), 3 (IQR 2–3), 2 (IQR 1–2) and 6 (IQR 4–8) weeks respectively. Delayed patient presentation to hospital was associated with significant adverse median survival 16 (IQR 11.5–22.5) weeks versus 20 (IQR 16–27.5) weeks, p = 0.004. Delay in initiating treatment was associated with significantly lower median survival 04 (IQR 4–6) weeks versus 06 (IQR 4–8) weeks, p = 0.003. Over 60% of both proximal and distal GCA presented at an advanced radiological stage (stage III/IV). The Kaplan Meier analysis showed that the higher hazard function was associated with a higher tumour stage and undergoing chemotherapy. Age of the patient and the treatment modality were significant predictors of the survival. Patient delay and delay in initiation of definitive treatment are the most important factors that adversely affect the outcomes of GCA. Public health interventions aiming to shorten the patient delay time with proper referral for specialist care would play an important role. Also, it is important to minimize these preventable delays and there should be time limits in producing the histopathology report and to establish online portals of hospital and laboratory information systems for easy access of histology reports in future.

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Human Epidermal Growth Factor Receptor-2 in Sri Lankan Gastric Carcinoma Patients with Clinicopathological Association and Survival

Abstract: GCa HER2 positivity was 9%, associated with a lower median overall survival. Adverse histological features had a positive correlation with HER2 positivity. These histological features could direct patients for confirmatory HER2 testing in limited resource settings.

Cited by 6 publications

References 48 publications

HER2 protein expression correlates with Lauren classification and P53 in gastric cancer patients

HER2 protein expression correlates with Lauren classification and P53 in gastric cancer patients

Human Epidermal Growth Factor Receptor-2(HER-2) expression in Sri Lankan gastric adenocarcinoma patients: An analysis of the concordance of HER2 expression and survival based on silver in-situ hybridization (SISH)

Delay in diagnosis to treatment and impact on survival of gastric adenocarcinoma in a low income setting without screening facility

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