Elsevier

Human Pathology

Volume 35, Issue 3, March 2004, Pages 309-316
Human Pathology

Original contribution
Chromosomal aberrations in esophageal squamous cell carcinoma among chinese: gain of 12p predicts poor prognosis after surgery

https://doi.org/10.1016/j.humpath.2003.10.020Get rights and content

Abstract

Sixty primary esophageal squamous cell carcinomas (ESCCs) were evaluated for cytogenetic changes by comparative genomic hybridization (CGH). Recurrent chromosomal aberrations were correlated with stage and clinical outcome after esophagectomy to identify cytogenetic changes that are of prognostic significance. Chromosomal aberrations were found in 52 (86.7%) cases. The most frequently detected chromosomal gains involved 3q (67.3%), 8q (57.7%), 5p (51.9%), 7q (28.8%), 15q (28.8%), 20p (21.2%), 20q (28.8%), 1q (26.9%), 7p (26.9%), 2p (23.1%), and 12p (23.1%). Chromosome 12p was most frequently involved in high-level amplification. Six of the 12 cases with gain in 12p showed high-level amplification and the minimum overlapping region localized to 12pter-p13. The most frequently detected chromosomal loss involved 3p (46.2%), 4q (26.9%), 4p (23.1%), 3q (19.2%), 9p (17.3%), 19p (17.3%), and whole 13 (15.4%). No significant correlation was found between the recurrent chromosomal aberrations and pathological stage of ESCC. Univariate analysis demonstrated that late pathological stage (III and IV), gain in 12p, and loss in 3p are associated with poor relapse-free survival. Multivariate analysis confirmed gain in 12p as independent prognosticator for relapse-free survival after esophagectomy besides pathological stage. We conclude that chromosomal aberrations are common in ESCC. Gain in 12p is indicative of poor prognosis after esophagectomy, and combined modality therapy would be indicated in these patients.

Section snippets

Primary tumor specimens and DNA extraction

Fresh specimens of primary tumor were collected after esophagectomy and stored at −80°C until DNA extraction. Specimens collected from 1994 to 1997 at Queen Mary Hospital, Hong Kong were included in this study. All patients were treated by surgery only, with esophagectomy and lymph node dissection; patients with preoperative or adjuvant postoperative chemotherapy or radiotherapy given were excluded. A total of 60 specimens were analyzed, all from ethnic Chinese patients. All specimens were

Results

Fifty-two of the 60 (86.7%) primary ESCCs exhibited chromosomal imbalances. Fig 1 shows the summarized CGH results. Fig 2 shows an example of the CGH ratio profiles. On average, there were 10.5 aberrations per tumor. The most frequently detected sites of DNA gains were 3q (35 cases; 67.3%), 8q (30 cases; 57.7%), and 5p (27 cases; 51.9%), with the minimal region of overlap in 3q26.2-qter, 8q23-qter, and 5pter-p14, respectively. Other chromosomal sites commonly demonstrating DNA gains included

Discussion

ESCC is a disease with poor prognosis; the overall 5-year survival after surgery alone is 5% to 20%. Studies have reported improved survival with combined modality treatment compared with radiotherapy or surgery alone.10, 11 However, more treatment brings additional toxicity and morbidity. If other markers besides stage can predict for prognosis, patients who are predicted to be at high risk for relapse after surgery alone can be selected for combined modality treatment. Those who would do well

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