This dissertation, "A Study of BARX2 Expression in Esophageal Squamous Cell Carcinoma" by Cheuk-man, Leung, 梁卓文, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author.
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.
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.
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).
BARX2 expression in ESCC was aberrant and mainly cytoplasmi