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Role of er, pr, her2 and egfr in esophageal carcinoma

Author: 
Muneera Gull, Zubaida Rasool, Danish Rafiq, Salma Gull, Salma Yaseen and Ishrat Younis
Subject Area: 
Health Sciences
Abstract: 

Introduction: Esophageal cancer is a serious malignancy with regards to mortality and prognosis. The incidence of esophageal adenocarcinoma is increasing in trends. In India, the extremely high incidence rates of esophageal cancer have been reported from the state of Jammu and Kashmir which seems to fall in the Asian esophageal-cancer belt particularly from Kashmir. The unique personal and dietary habits and environmental factors in Kashmir have been related to this high risk. Immunohistochemistry is nowadays a simple, reproducible way to assess the expression of oncogenic factors in paraffin embedded samples from cancer tissues. It is therefore more and more used customarily to study the expression of new potential therapeutic targets and to determine which patients are the most liable to answer to these specific therapies. Aiims and objectives: To study the expression of.ER/PR, EGFR and HER-2 in esophageal carcinoma.and to study the correlation of above mentioned markers with pathological characteristics such as tumor type, grade and lymph node status. Materials and Methods: It was a prospective study for a period of one and half years from June 2016 to December 2017 and retrospective study for three and half years from January 2013 to May 2016.The study was carried on resected specimens of esophagus over the period mentioned above. All esophageal carcinomas with or without nodal metastasis and other primary tumors of esophagus, tumors metastasized to esophagus and those who have received neoadjuvant therapy were taken. For the retrospective study, cases were taken from the records maintained in the Department of Pathology at SKIMS. Histopathological data was collected and relevant details were noted. Corresponding slides were collected and photographed wherever available. Prospective study comprised of fresh cases of esophageal carcinomas. In each case a brief clinical history was taken, along with other relevant investigations. The clinical data of the patient was recorded as per proforma. Samples were collected in 10% formalin for routine histopathological examination. After overnight fixation, the specimens were grossed with 3-4 sections taken from the tumor. Gross photographs of the specimen were taken. Sections from all resection margins were taken. The tissue was processed as per standard procedure for histological examination and 4-5 micron thick sections were cut on microtome and stained by routine haematoxylin and eosin stain. Immunohistochemistry was done in 30 Squamous cell carcinoma cases (out of a total of 86 cases) and all (12) Adenocarcinoma cases. After final microscopic diagnosis was made, the slides were photographed. Results: The study included a total of 98 cases received in our department and with the final diagnosis of esophageal carcinoma (SCC and AC). Out of 98 cases, 57 (58.2%) were males and 41 (41.8%) were females with a male to female ratio of 1.39:1. Age range was 35-75 years. The maximum number of cases was in the age group of 45-54 and 55-64 years and the least number of cases was seen in the age group of 35-44 years. Mean age was 55.9+8.92 years. Dysphagia was the main presenting complaint in majority of patients (69.4%). Most of the tumors presented as ulceroin filtrative lesions (25.5%). Most of the tumors were in the size range of 3-5 cm (49%). Middle 1/3rd of the esophagus was the most common site (48%) followed by lower 1/3rd (37.6%). Among the 98 esophagectomy cases, 83 (84.7%) were diagnosed as SCC, 12 as AC (12.2) and 3 (3.1%) as squamous cell carcinoma in situ. Most of the tumors were well and moderately differentiated. Regional lymph node involvement was present in 25% cases. Distant metastasis was not seen in any case.11 (11.2%) cases had CRM involved by the tumor. Out of the 83 cases of squamous cell carcinoma, 42 (50.6%) were T2, 39 (47.0%) were T3, 2 cases were in T1. Out of 12 AC cases, 11 (91.7%) were T3 and 1 (8.3%) was T2. Majority of the cases i.e.; 72 (73.5%) were in N0, 19 (19.4%) were in N1, 6 (6.1%) were in N2, 1 (1%) was in N3. Out of 86 SCC cases, 25 (29.1%) were in Stage IB, 24 (27.9%) were in stage IIA, 21 (24.4%) were in Stage IIB, 9 (10.5%) were in Stage IIIA, 3 (3.5%) were in Stage IIIB and 3 (3.5%) were in Stage 0. None of the cases was in Stage IV. One patient was in stage IA. Out of 12 AC cases, 7 (58.3%) cases were in Stage IIB, 3 (25%) cases were in Stage IIIB and 2 (16.7%) cases were in Stage IIIC. None of the cases was in Stage IV or Stage 0. Out of 98 esophagectomy cases, 32 (32.7%) had LVI and 29 (29.6%) had PNI. On immunohistochemistry; (IHC was done on 30 SCC and 12 AC cases), none of the 42 cases was positive for ERα or PR. For ERβ, among 12 adenocarcinoma cases, 9 cases were positive and among 30 SCC cases, 7 were positive. For EFGR, among 12 AC cases, 3 were positive and among 30 SCC cases, 17 were positive. For HER2, among 12 AC cases, 1 was positive and among 30 SCC cases, 2 were positive. Among 16 ERβ positive cases, 2 were in Grade 1, 7 in Grade 2 and 7 in Grade 3. None of the cases was of Grade 4. Among 20 EGFR positive cases, 3 were in Grade 1, 9 in Grade 2 and 8 in Grade 3. Among 3 HER2 positive cases, 1 was in Grade 1and 2 were in Grade 3. None of the cases was of Grade 2. ERβ positive cases were predominantly in N0 (8/16), followed by N2 (5/16). 2 cases were in N1 and 1 in N3. Among 20 EGFR positive cases, 7 were in N1, 6 in N2 and 7 in N0. Among 3 HER2 positive cases, 2 were in N0 and 1 was in N1. . Among the 16 ERβ positive cases, majority (7/16) were in Stage IIB. 3 were in Stage IIIB, 2 were in IIIC, 2 in IIIA and 2 in IB. None of the cases was in Stage IA or in Stage IV. Among the 20 EGFR positive cases, 7 cases were in Stage IIIA, 5 in Stage IIB, 3 in Stage IB, 3 in Stage IIIB, 1 in Stage IIA and 1 in Stage IIIC. . Among 3 HER2 positive cases, 2 were in Stage IIB and 1 in Stage IIA. ERβ expression had a significant correlation with tumor type. AC showed higher expression than SCC. EGFR had a significant correlation with tumor type, tumor grade and lymph node status. Summary and conclusion: The present study suggests that EGFR is a candidate for targeted therapy using anti-EGFR antibodies. Evaluation of EGFR overexpression detected by IHC may aid the selection of patients and prediction of sensitivity to adjuvant EGFR -targeted therapy for esophageal carcinoma. HER2 overexpression may also play a crucial role in the therapeutic management of both esophageal squamous cell carcinoma and esophageal adenocarcinoma. In present study, HER2 was positive in both ESCC and EAC. The sample size may have undermined statistical significance between HER2 and histopathological characteristics of esophageal carcinoma. Further studies may augment the understanding in this area.

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