Department of Pathology, Beaujon Hospital, 92110 Clichy, France.
Hum Pathol. 2011 Nov;42(11):1702-9. doi: 10.1016/j.humpath.2011.01.015. Epub 2011 Apr 29.
The ability to predict response after chemoradiotherapy in rectal adenocarcinoma may allow selecting patients to whom less invasive surgical treatment could be proposed. Tumor hypoxia has been implicated in the mechanisms of resistance to chemoradiotherapy in several malignancies. The aim was to identify morphological criteria and molecular markers of hypoxia associated with chemoradiotherapy response. Clinicopathologic data from 61 patients (35 male, 60.5 ± 10 years) undergoing rectal cancer resection after neoadjuvant chemoradiotherapy were collected. Pretreatment biopsies, available for 40 patients, were immunostained for hypoxia markers (carbonic anhydrase 9, glucose transporter 1, chemokine receptor 4) and microvascular density determination. Mean tumor size was 2.7 ± 1.6 cm. Twenty-one patients (34%) were considered as responders, that is, having significant or complete primary tumor regression without lymph node metastasis. Compared to other patients, responders had significantly more often flat tumors with or without ulceration (57% versus 18%, P = .01) and less vascular and/or neural invasions (9% versus 65%, P < .0001) or tumor necrosis (9% versus 41%, P < .01), respectively. Regarding pretreatment biopsies, carbonic anhydrase 9 expression was significantly lower in responders (7% versus 46%, P = .012). This study showed that tumor necrosis as an overexpression of carbonic anhydrase 9 was an effective molecular marker of postchemoradiotherapy response. This might suggest a key role of hypoxia in resistance mechanisms of chemoradiotherapy in rectal adenocarcinoma. This study highlighted the importance of predictive criteria to chemoradiotherapy response in proposing to selected patients an alternative treatment (eg, local resection) to more radical surgery.
在直肠腺癌中，预测放化疗后的反应能力可能使我们能够选择更具侵袭性的手术治疗的患者。肿瘤缺氧已被认为是多种恶性肿瘤对放化疗抵抗的机制之一。目的是确定与放化疗反应相关的缺氧形态学标准和分子标志物。收集了 61 例接受新辅助放化疗后直肠腺癌切除术的患者（35 例男性，60.5±10 岁）的临床病理数据。对 40 例患者的预处理活检标本进行了缺氧标志物（碳酸酐酶 9、葡萄糖转运蛋白 1、趋化因子受体 4）和微血管密度测定的免疫染色。肿瘤平均大小为 2.7±1.6cm。21 例患者（34%）被认为是有反应者，即没有淋巴结转移的原发性肿瘤有显著或完全消退。与其他患者相比，有反应者更常出现平坦的肿瘤，伴有或不伴有溃疡（57%比 18%，P=0.01），血管和/或神经浸润（9%比 65%，P<0.0001）或肿瘤坏死（9%比 41%，P<0.01）的情况较少。关于预处理活检标本，碳酸酐酶 9 的表达在有反应者中明显较低（7%比 46%，P=0.012）。本研究表明，肿瘤坏死和碳酸酐酶 9 的过表达是放化疗后反应的有效分子标志物。这可能表明缺氧在直肠腺癌放化疗抵抗机制中起关键作用。本研究强调了预测放化疗反应的重要性，以向选定的患者提出替代治疗（例如局部切除术）以取代更激进的手术。
