A study of BARX2 expression in esophageal squamous cell carcinoma

Abstract

Background

Esophageal carcinoma mainly affects middle aged to elderly males. It ranks the

ninth most common cancer world-wide. The main histological types are squamous

cell carcinoma and adenocarcinoma. In Hong Kong, esophagus squamous cell

carcinoma (ESCC) is by far the more common. BARX2 is a human homeobox gene

located at 11q24-q25, encoding a protein of 254 amino acids. Recent researches show

that its expression in breast cancer promotes cellular invasion.

Objectives

The study aimed to test the hypothesis that BARX2 is a prognostic marker in

ESCC. BARX2 expression in ESCC was correlated with patient survival and other

clinicopathologic parameters in a cohort of patients.

Material and Methods

Records of ESCC patients were obtained retrospectively from the computerized

database of Queen Mary Hospital. ESCC patients, who underwent esophagectomy in

the hospital from 1998 to 2005 but without receiving prior chemotherapy or

radiotherapy directed to the tumor, were selected. Tumor staging was done according

to the 6th edition of AJCC Cancer Staging Manual. Immunohistochemical staining

for BARX2 expression was performed on paraffin sections of the primary ESCC

tissues sampled in a tissue microarray constructed for research purposes. The pattern

of BARX2 expression in nucleus and cell cytoplasm of tumor cells was recorded and

the staining intensity scored on a 4-point scale. The scores were statistically analyzed

together with the various clinicopathologic parameters. BARX2 expression and

patient survival time were analyzed by the log-rank test.

Results

A total of 78 ESCC patients were recruited. At the time of data analysis, 52

(66.7%) patients were dead. The overall median survival of patients was 14.3 months.

BARX2 was found to be mainly expressed in the cytoplasm of tumor cells while

non-tumor epithelium showed strong nuclear expression. Patients with high level

BARX2 expression had short survival time, though the difference did not reach

statistical significance (p=0.075). Within the subgroup of lower T-stage ESCC (T1-3),

high level BARX2 expression was significantly associated with shorter survival time

(p=0.042). However, differential BARX2 expression did not affect survival time

within the group of patients who had advanced stage (T4) disease (p=0.525). In

patients who had no regional lymph node metastasis (N0), high level BARX2

expression was associated with shorter survival time (p=0.023). However, when

patients had regional lymph node metastases (N1), BARX2 expression did not affect

patient survival time (p=0.533). Patients whose ESCC showed moderate

differentiation in a three-tier tumor grading system, when accompanied with low level

BARX2 expression, had longer survival time (p=0.029). However, BARX2

expression did not affect survival time when ESCC showed either well differentiation

(p=0.462) or poor differentiation (p=0.637). Multivariate analysis showed patient age

and T-stage to be the only two independent parameters of prognostic significance

(p=0.025 and p=0.036 respectively).

Conclusions

BARX2 expression in ESCC was aberrant and mainly cytoplasmic. It was

inversely correlated with patient survival time in early ESCC disease (T1-T3 or N0).

BARX2 expression evaluated by immunohistochemistry could be a useful and

practical prognostic marker of ESCC in its early stages, when the proper decision on

treatment would be critical for the patients.