This preprint is under consideration at Journal of Gastrointestinal Cancer. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research Article
Duminda Subasinghe
Department of Surgery,University of Colombo
Corresponding Author
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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.
Keywords
Gastric carcinoma, HER2, SISH, IHC, Survival, Concordance
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This preprint is under consideration at Journal of Gastrointestinal Cancer. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Duminda Subasinghe
Department of Surgery,University of Colombo
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 17 Mar, 2021
No community comments so far
Reviewers invited
Invitations sent on 08 Mar, 2021
Editor assigned
On 05 Mar, 2021
First submitted
On 03 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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