Prognostic and Predictive Value of Selected Biologic Markers in Locally Advanced Rectal Adeno-carcinoma Treated with Neoadjuvant Chemo-radiotherapy
Background: Factors that predict tumour response to preoperative
chemoradiation in rectal cancer patients have not been well studied.
Certain biologic predictors may be useful to select patients who need more
or less aggressive approach.
Aim: The objective of this study is to investigate the prognostic utility of
MIB-1, p53, cyclin D1, Her2/neu, EGFR and COX-2 in locally advanced
rectal adenocarcinoma as predictors of response to neoadjuvant chemoradiotherapy.
Material and Methods: The present work included 45 pretreatment
colonscopic biopsies from patients with locally advanced rectal
adenocarcinoma (T3-T4) who were treated with neoadjuvant
chemoradiation, followed by either abdomino-perineal resection or by low
anterior resection with total mesorectal excision. Pathologic response was
classified into complete, partial and poor response.
Formalin fixed paraffin embedded sections of the 45 specimens were
immunostained for MIB-1, p53, cyclin D1, Her2/neu, EGFR and COX-2.
Results: Complete pathologic response was seen in 7/45 (16%), partial
response in 8/45 (18%), and no/poor response in 30/45 (67%) patients.
None of the clinical or pathologic variables in the pretreatment biopsy was
correlated with complete or partial pathologic response. Overexpression of
COX-2 was found in 30/45 (67%) cases and demonstrated significant
correlation with lymphovascular invasion, depth of invasion, tumor stage,
recurrence, and no/poor pathologic response (P< 0.05). EGFR was
positive in 28/45 (62%) cases and was correlated with distant metastases
and local recurrence (P< 0.05). Her2/neu was detected in 5/45 (11%) cases
and also showed significant correlation with distant metastasis. Other
markers showed no significant correlation with pathologic response or
other pathologic parameters.
Conclusion: Our findings concluded that overexpression of COX-2 in the
pretreatment biopsy correlates with poor response to neoadjuvant
chemoradiotherapy in locally advanced rectal adenocarcinoma patients.
EGFR and Her2/neu also showed prognostic significance correlation with
local recurrence and/or distant metastases.
Key Words: Rectal adenocarcinoma, Immunohistochemistry, COX-2, EGFR & Her 2/neu