Human Epidermal Growth Factor Receptor 2 [HER‐2/neu] Amplification and Microsatellite Stable Status in Gastric and Gastroesophageal Adenocarcinoma: Assessing Frequency and Prognostic Implications at the Cancer Institute of Iran
ABSTRACT Background Molecular targeted therapy and immunotherapy have shown promise in managing gastric adenocarcinoma. The amplified expression of Human epidermal growth factor receptor‐2 (HER‐2) and microsatellite stable (MSI) status serve as indicators of response to targeted therapy and immunoth...
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Wiley
2025-08-01
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| Series: | Cancer Reports |
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| Online Access: | https://doi.org/10.1002/cnr2.70314 |
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| author | Samaneh Salarvand Abbas Mohammadi Reza Shahsiah Farzaneh Bagheri Mahsa Gholizadeh Somayeh Jolany‐Vangah Ebrahim Esmati Marzieh Lashkari Vahid Soleymani Seraj Zareh‐Dehabadi Vahid Mehrtash Amirmohsen Jalaeefar Mohammad Shirkhoda Moones Toosang Romina Abyaneh Reza Ghalehtaki |
| author_facet | Samaneh Salarvand Abbas Mohammadi Reza Shahsiah Farzaneh Bagheri Mahsa Gholizadeh Somayeh Jolany‐Vangah Ebrahim Esmati Marzieh Lashkari Vahid Soleymani Seraj Zareh‐Dehabadi Vahid Mehrtash Amirmohsen Jalaeefar Mohammad Shirkhoda Moones Toosang Romina Abyaneh Reza Ghalehtaki |
| author_sort | Samaneh Salarvand |
| collection | DOAJ |
| description | ABSTRACT Background Molecular targeted therapy and immunotherapy have shown promise in managing gastric adenocarcinoma. The amplified expression of Human epidermal growth factor receptor‐2 (HER‐2) and microsatellite stable (MSI) status serve as indicators of response to targeted therapy and immunotherapy, respectively. Aims This study assessed the frequency of MSI status and HER‐2 expression in a pretreated sample of Iranian patients with gastric and gastroesophageal (GE) adenocarcinoma. Methods and Results We conducted HER‐2/neu expression and mismatch repair (MMR) system analyses on specimens from patients with gastric and GE adenocarcinoma at the Cancer Institute of Iran. Archival tissues from 135 mainly pre‐treated surgical specimens of gastric adenocarcinoma cases were used for HER‐2 analysis, and 66 specimens were used for MSI analysis. All specimens were tested for HER‐2 amplification, revealing that 11 patients (8.1%) had HER‐2 amplification, and three out of 66 examined patients exhibited MSI‐H. Patients with HER‐2 overexpressed specimens had a shorter median overall survival (OS) compared with HER‐2 negative cases (21 months (95% CI: 1.4–40.6) vs. 31 months (95% CI: 22.9–39), p = 0.18). The median disease‐free survival (DFS) for HER‐2 positive and negative patients was 15 and 28 months, respectively (p = 0.25). The estimated median OS and DFS for patients with negative MSI were 26 and 20 months, respectively. However, none of the patients with MSI‐positive status experienced recurrence, metastases, or death within the follow‐up period; thus, MSI‐H patients had a significantly improved OS and DFS (p = 0.018 and 0.020). Conclusion HER‐2 expression, while less common in our Iranian population compared with North American or Western European countries, showed a nonsignificant trend toward poor outcomes in patients with gastric adenocarcinoma. MSI‐H status was highly infrequent in our population, suggesting that immunotherapy may not be a beneficial treatment for a significant fraction of Iranian patients with gastric adenocarcinoma. However, a minority may still benefit from it. MSI‐H was associated with reduced perineural invasion and improved OS and DFS. Therefore, this hypothesis warrants further investigation in clinical trials to underscore the prognostic significance of HER‐2 and MSI status and the value of molecular profiling in guiding personalized treatment strategies. |
| format | Article |
| id | doaj-art-1808b9e8248d45c1b99f3fbc04ece09b |
| institution | Kabale University |
| issn | 2573-8348 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
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| series | Cancer Reports |
| spelling | doaj-art-1808b9e8248d45c1b99f3fbc04ece09b2025-08-26T06:00:41ZengWileyCancer Reports2573-83482025-08-0188n/an/a10.1002/cnr2.70314Human Epidermal Growth Factor Receptor 2 [HER‐2/neu] Amplification and Microsatellite Stable Status in Gastric and Gastroesophageal Adenocarcinoma: Assessing Frequency and Prognostic Implications at the Cancer Institute of IranSamaneh Salarvand0Abbas Mohammadi1Reza Shahsiah2Farzaneh Bagheri3Mahsa Gholizadeh4Somayeh Jolany‐Vangah5Ebrahim Esmati6Marzieh Lashkari7Vahid Soleymani8Seraj Zareh‐Dehabadi9Vahid Mehrtash10Amirmohsen Jalaeefar11Mohammad Shirkhoda12Moones Toosang13Romina Abyaneh14Reza Ghalehtaki15Department of Clinical and Anatomical Pathology, Cancer Institute, School of Medicine Tehran University of Medical Sciences Tehran IranDepartment of Ophthalmology, School of Medicine Ahvaz Joundishapur University of Medical Sciences Ahvaz IranDepartment of Clinical and Anatomical Pathology, Cancer Institute, School of Medicine Tehran University of Medical Sciences Tehran IranDepartment of Radiation Oncology, Cancer Institute, IKHC, School of Medicine Tehran University of Medical Sciences Tehran IranDepartment of Radiation Oncology, Cancer Institute, IKHC, School of Medicine Tehran University of Medical Sciences Tehran IranDepartment of Radiation Oncology, Cancer Institute, IKHC, School of Medicine Tehran University of Medical Sciences Tehran IranDepartment of Radiation Oncology, Cancer Institute, IKHC, School of Medicine Tehran University of Medical Sciences Tehran IranRadiation Oncology Research Center, Cancer Research Institute Tehran University of Medical Sciences Tehran IranDepartment of Clinical and Anatomical Pathology, Cancer Institute, School of Medicine Tehran University of Medical Sciences Tehran IranRadiation Oncology Research Center, Cancer Research Institute Tehran University of Medical Sciences Tehran IranDepartment of Clinical and Anatomical Pathology, Cancer Institute, School of Medicine Tehran University of Medical Sciences Tehran IranDepartment of Oncosurgery, Cancer Institute, IKHC Tehran University of Medical Sciences Tehran IranDepartment of Oncosurgery, Cancer Institute, IKHC Tehran University of Medical Sciences Tehran IranDepartment of Clinical and Anatomical Pathology, Cancer Institute, School of Medicine Tehran University of Medical Sciences Tehran IranRadiation Oncology Research Center, Cancer Research Institute Tehran University of Medical Sciences Tehran IranDepartment of Radiation Oncology, Cancer Institute, IKHC, School of Medicine Tehran University of Medical Sciences Tehran IranABSTRACT Background Molecular targeted therapy and immunotherapy have shown promise in managing gastric adenocarcinoma. The amplified expression of Human epidermal growth factor receptor‐2 (HER‐2) and microsatellite stable (MSI) status serve as indicators of response to targeted therapy and immunotherapy, respectively. Aims This study assessed the frequency of MSI status and HER‐2 expression in a pretreated sample of Iranian patients with gastric and gastroesophageal (GE) adenocarcinoma. Methods and Results We conducted HER‐2/neu expression and mismatch repair (MMR) system analyses on specimens from patients with gastric and GE adenocarcinoma at the Cancer Institute of Iran. Archival tissues from 135 mainly pre‐treated surgical specimens of gastric adenocarcinoma cases were used for HER‐2 analysis, and 66 specimens were used for MSI analysis. All specimens were tested for HER‐2 amplification, revealing that 11 patients (8.1%) had HER‐2 amplification, and three out of 66 examined patients exhibited MSI‐H. Patients with HER‐2 overexpressed specimens had a shorter median overall survival (OS) compared with HER‐2 negative cases (21 months (95% CI: 1.4–40.6) vs. 31 months (95% CI: 22.9–39), p = 0.18). The median disease‐free survival (DFS) for HER‐2 positive and negative patients was 15 and 28 months, respectively (p = 0.25). The estimated median OS and DFS for patients with negative MSI were 26 and 20 months, respectively. However, none of the patients with MSI‐positive status experienced recurrence, metastases, or death within the follow‐up period; thus, MSI‐H patients had a significantly improved OS and DFS (p = 0.018 and 0.020). Conclusion HER‐2 expression, while less common in our Iranian population compared with North American or Western European countries, showed a nonsignificant trend toward poor outcomes in patients with gastric adenocarcinoma. MSI‐H status was highly infrequent in our population, suggesting that immunotherapy may not be a beneficial treatment for a significant fraction of Iranian patients with gastric adenocarcinoma. However, a minority may still benefit from it. MSI‐H was associated with reduced perineural invasion and improved OS and DFS. Therefore, this hypothesis warrants further investigation in clinical trials to underscore the prognostic significance of HER‐2 and MSI status and the value of molecular profiling in guiding personalized treatment strategies.https://doi.org/10.1002/cnr2.70314AdenocarcinomaDNA mismatch repairGastric neoplasmHER family receptor |
| spellingShingle | Samaneh Salarvand Abbas Mohammadi Reza Shahsiah Farzaneh Bagheri Mahsa Gholizadeh Somayeh Jolany‐Vangah Ebrahim Esmati Marzieh Lashkari Vahid Soleymani Seraj Zareh‐Dehabadi Vahid Mehrtash Amirmohsen Jalaeefar Mohammad Shirkhoda Moones Toosang Romina Abyaneh Reza Ghalehtaki Human Epidermal Growth Factor Receptor 2 [HER‐2/neu] Amplification and Microsatellite Stable Status in Gastric and Gastroesophageal Adenocarcinoma: Assessing Frequency and Prognostic Implications at the Cancer Institute of Iran Cancer Reports Adenocarcinoma DNA mismatch repair Gastric neoplasm HER family receptor |
| title | Human Epidermal Growth Factor Receptor 2 [HER‐2/neu] Amplification and Microsatellite Stable Status in Gastric and Gastroesophageal Adenocarcinoma: Assessing Frequency and Prognostic Implications at the Cancer Institute of Iran |
| title_full | Human Epidermal Growth Factor Receptor 2 [HER‐2/neu] Amplification and Microsatellite Stable Status in Gastric and Gastroesophageal Adenocarcinoma: Assessing Frequency and Prognostic Implications at the Cancer Institute of Iran |
| title_fullStr | Human Epidermal Growth Factor Receptor 2 [HER‐2/neu] Amplification and Microsatellite Stable Status in Gastric and Gastroesophageal Adenocarcinoma: Assessing Frequency and Prognostic Implications at the Cancer Institute of Iran |
| title_full_unstemmed | Human Epidermal Growth Factor Receptor 2 [HER‐2/neu] Amplification and Microsatellite Stable Status in Gastric and Gastroesophageal Adenocarcinoma: Assessing Frequency and Prognostic Implications at the Cancer Institute of Iran |
| title_short | Human Epidermal Growth Factor Receptor 2 [HER‐2/neu] Amplification and Microsatellite Stable Status in Gastric and Gastroesophageal Adenocarcinoma: Assessing Frequency and Prognostic Implications at the Cancer Institute of Iran |
| title_sort | human epidermal growth factor receptor 2 her 2 neu amplification and microsatellite stable status in gastric and gastroesophageal adenocarcinoma assessing frequency and prognostic implications at the cancer institute of iran |
| topic | Adenocarcinoma DNA mismatch repair Gastric neoplasm HER family receptor |
| url | https://doi.org/10.1002/cnr2.70314 |
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