Biopsy specimen microvessel density is a useful prognostic marker in patients with T(2-4)M(0) esophageal cancer treated with chemoradiotherapy.
OBJECTIVE
The purpose of this study was to identify prognostic markers for chemoradiotherapy (CRT) in T(2-4)M(0) esophageal cancer.


METHODS
We investigated clinicopathological and biological markers in biopsy specimens from 73 T(2-4)M(0) esophageal cancer patients treated with CRT (5-fluorouracil plus cisplatin and 60 Gy of radiation). Expressions of p53 gene product, Ki-67 labeling index, epidermal growth factor receptor, cyclin D1, vascular endothelial growth factor, microvessel density (MVD), thymidylate synthase, dihydropyrimidine dehydrogenase, and glutathione S-transferase pi in formalin-fixed biopsy samples of primary tumors before CRT were examined immunohistochemically. Clinicopathological and biological marker expressions were compared in terms of survival.


RESULTS
Univariate analysis revealed that performance status and T stage in clinicopathological features had a significant association with survival (P = 0.007 and 0.04, respectively) and that patients whose tumors showed high MVD [>median (19.7 vessels)] in biological markers had significantly better survival than those with low MVD (< or = median, P = 0.02). Also, there were weak associations of p53 and Ki-67 with survival (P = 0.08 and 0.07, respectively). Multivariate analysis, using both clinicopathological and biological markers, showed that MVD, T stage, and performance status became independent variables (P = 0.002, 0.02, and 0.02, respectively). Kaplan-Meier analysis showed that the patients with high MVD tumors survived longer than those with low MVD tumors (median survival time, not reached and 13 months, respectively; 3-year survival rate, 61% and 33%, respectively), with a significant difference of P = 0.02.


CONCLUSIONS
These results indicate that MVD using pretreatment biopsy specimens is a potentially useful prognostic marker for CRT in patients with T(2-4)M(0) esophageal cancer who are treated with CRT.
Hironaka
Shuichi
S
Pathology Division, National Cancer Center Research Institute East, Chiba 277-8577, Japan.
Hasebe
Takahiro
T
Kamijo
Tomoyuki
T
Ohtsu
Atsushi
A
Boku
Narikazu
N
Yoshida
Shigeaki
S
Saitoh
Hiroki
H
Ochiai
Atsushi
A
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D019938:Cyclin D1 / Q000378:metabolism; D042943:Dihydrouracil Dehydrogenase (NADP); D016228:Endothelial Growth Factors / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000098:blood supply* / Q000401:mortality / Q000628:therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D010088:Oxidoreductases / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011829:Radiation Dosage; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D007527:Isoenzymes; D019394:Ki-67 Antigen; D008222:Lymphokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019938:Cyclin D1; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D066246:ErbB Receptors; D002945:Cisplatin; D005472:Fluorouracil