title: Genetic features of metachronous esophageal cancer developed in Hodgkin's lymphoma or breast cancer long-term survivors: an exploratory study.
abstract: BACKGROUND
  Development of novel therapeutic drugs and regimens for cancer treatment has led to improvements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received regional radiotherapy for Hodgkin's Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemiological studies, little information is available on the genetic changes involved in the pathogenesis of these solid therapy-related neoplasms.
  
  
  METHODS
  Using microsatellite markers located in 7 chromosomal regions frequently deleted in sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esophageal 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 different higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of the genetic determinants located nearby these regions in the development of the two esophageal cancer histotypes.
  
  
  CONCLUSIONS
  Altogether, our results strengthen the genetic diversity among ESCC and EADC whether they occurred spontaneously or after therapeutic treatments. The presence of histotype-specific alterations in esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests that their transformation process, though the putative different etiological origin, may retrace sporadic ESCC and EADC carcinogenesis.
authors.affiliation: Immunology and Molecular Oncology, Veneto Institute of Oncology, IOV-IRCCS, Padova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Boldrin
authors.affiliation: Immunology and Molecular Oncology, Veneto Institute of Oncology, IOV-IRCCS, Padova, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Rumiato
authors.affiliation: Department of Medicine, Surgical Pathology and Cytopathology, University of Padova, Padova, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Medicine, Surgical Pathology and Cytopathology, University of Padova, Padova, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Cappellesso
authors.affiliation: Department of Medicine, Surgical Pathology and Cytopathology, University of Padova, Padova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.affiliation: Medical Oncology, Veneto Institute of Oncology, IOV-IRCCS, Padova, Italy.
authors.forename: Vanna
authors.initials: V
authors.lastname: Chiarion-Sileni
authors.affiliation: Department of Surgical Sciences, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ruol
authors.affiliation: Oncological Surgery, Veneto Institute of Oncology, IOV-IRCCS, Padova, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Alfieri
authors.affiliation: Oncological Surgery, Veneto Institute of Oncology, IOV-IRCCS, Padova, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cagol
authors.affiliation: Oncological Surgery, Veneto Institute of Oncology, IOV-IRCCS, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Castoro
authors.affiliation: Immunology and Molecular Oncology, Veneto Institute of Oncology, IOV-IRCCS, Padova, Italy; Department of Surgical Sciences, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Amadori
authors.affiliation: Immunology and Molecular Oncology, Veneto Institute of Oncology, IOV-IRCCS, Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Saggioro
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D006689:Hodgkin Disease / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics*; D017741:Survivors