Rasheed S, Harris A L, Tekkis P P, Turley H, Silver A, McDonald P J, Talbot I C, Glynne-Jones R, Northover J M A, Guenther T
Department of Surgery, St Mark's Hospital, Harrow, Middlesex, UK.
Pathol Res Pract. 2009;205(1):1-9. doi: 10.1016/j.prp.2008.08.008. Epub 2008 Nov 13.
The mechanism by which neoplasias respond to hypoxia determines their biological behavior and prognosis. Understanding the biology of tumors under hypoxic conditions is crucial for the development of anti-angiogenic therapy. Using the largest cohort of rectal adenocarcinomas to date, this study aimed to assess microvessel density (MVD) and carbonic anhydrase-9 (CA-9) expression and to correlate the results with recurrence and cancer-specific survival.
Patients (n=101) who underwent surgery for rectal adenocarcinoma without previous neoadjuvant therapy or metastatic disease were selected. MVD and CA-9 expression were assessed immunohistologically by using the CD34 antibody and the MN/CA9 M75 antibody, respectively. In a multifactorial analysis, the results were correlated with tumor stage, recurrence rate, and long-term survival.
MVD was higher with increased T- and N-stages (p<0.01) and associated positively with poor survival (hazard ratio (HR) 1.3 per 10 vessel increase, p<0.01). CA-9 was expressed in 73% of cancers. Negative lymph node status correlated with CA-9 positivity (p<0.05), reflected in a higher rate of CA-9 positivity in earlier Dukes' stages (p<0.05). CA-9 positivity across tumor node metastasis (TNM) stages approached significance (Stage I/II: 80% CA-9 positive vs. 20% CA-9 negative; Stage III: 63% CA-9 positive vs. 37% negative, p=0.051). A trend was seen towards better cancer-specific survival in patients with CA-9 positive carcinomas (HR 0.51, p=0.07) on univariate analysis.
MVD was higher in more advanced T- and N-stages and may be used as a determinant of survival in patients with rectal adenocarcinomas. CA-9 expression was seen more often in earlier Dukes' stages, possibly representing an early tumor hypoxic response. CA-9 expression by adenocarcinoma cells may confer long-term survival advantage in surgically treated rectal cancer.
肿瘤对缺氧的反应机制决定其生物学行为和预后。了解缺氧条件下肿瘤的生物学特性对于抗血管生成治疗的发展至关重要。本研究使用了迄今为止最大的直肠腺癌队列，旨在评估微血管密度（MVD）和碳酸酐酶9（CA-9）的表达，并将结果与复发和癌症特异性生存率相关联。
选取101例接受直肠腺癌手术且未接受过新辅助治疗或转移性疾病的患者。分别使用CD34抗体和MN/CA9 M75抗体通过免疫组织化学方法评估MVD和CA-9表达。在多因素分析中，将结果与肿瘤分期、复发率和长期生存率相关联。
MVD随着T分期和N分期的增加而升高（p<0.01），并且与不良生存率呈正相关（每增加10个血管的风险比（HR）为1.3，p<0.01）。73%的癌症中表达CA-9。阴性淋巴结状态与CA-9阳性相关（p<0.05），这在早期杜克分期中CA-9阳性率较高中得到体现（p<0.05）。跨肿瘤淋巴结转移（TNM）分期的CA-9阳性接近显著水平（I/II期：80% CA-9阳性对20% CA-9阴性；III期：63% CA-9阳性对37%阴性，p=0.051）。单因素分析显示，CA-9阳性癌患者的癌症特异性生存率有改善趋势（HR 0.51，p=0.07）。
在更晚期的T分期和N分期中MVD更高，并且可作为直肠腺癌患者生存率的一个决定因素。CA-9表达更多见于早期杜克分期，可能代表早期肿瘤缺氧反应。腺癌细胞的CA-9表达可能在手术治疗的直肠癌中赋予长期生存优势。
