Assessment of Chromosomal Aberrations and S-phase Fraction in Patients With Esophageal Cancer.

INTRODUCTION

The varying pace of cell proliferation influences cancer development and persistent growth. S-phase fraction (SPF) refers to the percentage of cells in a tumor in the cell cycle phase, during which DNA is synthesized. SPF has been correlated with nuclear grade, tumor size, estrogen receptor, progesterone receptor, metastasis, and clinical response to neoadjuvant chemotherapy. Aberrations in the number and structure of chromosomes are a common feature of cells from solid tumors. The evaluation of the frequency of chromosomal aberrations in peripheral lymphocytes has been reported as a sensitive cytogenetic assay indicating cancer progression, especially in blood cancer. The present study assessed the correlation between chromosomal aberrations in peripheral blood lymphocytes (PBL) and SPF in the tumor tissue of esophageal cancer patients.

MATERIALS AND METHODS

The present study included 172 subjects, 86 esophageal cancer patients and 86 unrelated age-gender-matched healthy controls. Cytogenetic analysis was done in 172 subjects after 72 hours of peripheral lymphocyte culturing and Giemsa-Trypsin Giemsa banding. SPF was performed in 86 tissue/biopsy samples of esophageal cancer patients using the in vitro bromodeoxyuridine technique.

RESULTS

Chromosomal aberrations were higher in esophageal cancer patients than in healthy controls. The mean (%) aberrant metaphases were significantly higher in patients (35.5 ± 13.3) than in controls (16.0 ± 6.6; p<0.0001). Similarly, mean (%) metaphases with structural aberrations were 16.3 ± 12.0 in patients versus 7.6 ± 5.0 in controls (p<0.0001), while mean (%) metaphases with numerical aberrations were 14.5 ± 7.4 in patients compared to 7.3 ± 4.3 in controls (p<0.0001), and mean (%) metaphases with both structural and numerical aberrations in patients were 4.8 ± 3.5 versus 1.1 ± 1.3 in controls (p<0.0001). Karyotype analysis revealed a higher frequency of chromosomal aberrations, including loss, gain, break, gap, deletion, addition, and translocations, affecting chromosomes 5, 6, 7, 8, 9, 10, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, X, and Y in esophageal cancer patients. The mean SPF for stage I, stage II, stage III, and stage IV was 8.0±5.0, 8.2±4.8, 8.7 ± 4.2, and 10.8 ± 6.7, respectively. There was no significant difference in the mean SPF among different stages of esophageal cancer patients. However, it was in concordance with the pathological stage of the patients being lowest for the stage I patients and highest for the stage IV patients. The chromosomal aberrations in PBL were also lower in stage I (10%) and higher in stage IV (67%) patients.

CONCLUSIONS

Chromosomal aberrations obtained in lymphocytes of esophageal cancer patients showed highly significant differences from those of unrelated healthy controls. The SPF values were higher during the disease progression, with a corresponding high and increasing chromosomal instability in lymphocytes.