RESEARCH ARTICLE Genetic Features of Metachronous Esophageal Cancer Developed in Hodgkin’s Lymphoma or Breast Cancer Long-Term Survivors: An Exploratory Study

Background Development of novel therapeutic drugs and regimens for cancer treatment has led to im-provements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received re-gional radiotherapy for Hodgkin’s Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemio-logical studies, little information is available on the genetic changes involved in the patho-genesis of these solid therapy-related neoplasms. Methods Using microsatellite markers located in 7 chromosomal regions frequently deleted in spo-radic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esoph-ageal carcinoma developed in HL or breast cancer long-term survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while 26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11 EADC). Results We found that, though the overall LOH frequency at the studied chromosomal regions was similar among metachronous and sporadic tumors, the latter exhibited a statistically differ-ent higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we ob-served that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EAD