Sato Hiro, Suzuki Yoshiyuki, Ide Munenori, Katoh Toshihide, Noda Shin-Ei, Ando Ken, Oike Takahiro, Yoshimoto Yuya, Okonogi Noriyuki, Mimura Kousaku, Asao Takayuki, Kuwano Hiroyuki, Nakano Takashi
Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan.
PLoS One. 2014 Sep 26;9(9):e108122. doi: 10.1371/journal.pone.0108122. eCollection 2014.
Enhancing immunologic responses, including human leukocyte antigen (HLA) class I expression on tumor cells and recognition and elimination of tumor cells by tumor-specific cytotoxic T lymphocyte (CTL), is considered a novel concept of radiotherapy. The present study examined patients who underwent preoperative hyperthermo-chemoradiotherapy (HCRT) for locally advanced rectal cancer to assess the correlation between HLA class I expression and clinical outcome.
Seventy-eight patients with locally advanced rectal adenocarcinoma who received preoperative HCRT were enrolled. The median age of the patients was 64 years (range, 33-85 years) and 4, 18, and 56 patients had clinical stage I, II and III disease, respectively. Formalin-fixed and paraffin-embedded tissues excised before and after HCRT were subjected to immunohistochemical analysis with an anti-HLA class I-A, B, C antibody. HLA class I expression was graded according to tumor cell positivity.
In pre-HCRT, the number of specimens categorized as Grade 0 and 1 were 19 (24%) and 58 (74%), respectively. Only 1 patient (1%) showed Grade 2 expression. However, 6 (8%), 27 (35%), 7 (9%), and 12 (15%) post-HCRT specimens were graded as Grade 0, 1, 2, and 3, respectively. There was a significant increase in HLA class I expression in post-HCRT specimens (p<0.01). However, neither pre- nor post-HCRT HLA class I expression affected overall survival and distant metastasis-free survival in clinical stage III patients. Univariate analysis revealed that Post-HCRT HLA class I expression showed a significant negative relationship with LC (p<0.05). Nevertheless, multivariate analysis showed that there was no correlation between HLA class I expression and clinical outcome.
HCRT increased HLA class I expression in rectal cancer patients. However, multivariate analysis failed to show any correlation between the level of HLA class I expression and prognosis.
增强免疫反应,包括肿瘤细胞上人类白细胞抗原(HLA)I类分子的表达以及肿瘤特异性细胞毒性T淋巴细胞(CTL)对肿瘤细胞的识别和清除,被认为是放射治疗的一个新概念。本研究对接受术前热化疗放疗(HCRT)的局部晚期直肠癌患者进行了检查,以评估HLA I类分子表达与临床结果之间的相关性。
纳入78例接受术前HCRT的局部晚期直肠腺癌患者。患者的中位年龄为64岁(范围33 - 85岁),分别有4例、18例和56例患者处于临床I期、II期和III期。对HCRT前后切除的福尔马林固定石蜡包埋组织进行抗HLA I类A、B、C抗体的免疫组织化学分析。根据肿瘤细胞阳性情况对HLA I类分子表达进行分级。
在HCRT前,分类为0级和1级的标本数量分别为19例(24%)和58例(74%)。仅1例患者(1%)表现为2级表达。然而,HCRT后标本分级为0级、1级、2级和3级的分别有6例(8%)、27例(35%)、7例(9%)和12例(15%)。HCRT后标本中HLA I类分子表达显著增加(p<0.01)。然而,HCRT前后的HLA I类分子表达均未影响临床III期患者的总生存期和无远处转移生存期。单因素分析显示,HCRT后HLA I类分子表达与局部控制(LC)呈显著负相关(p<0.05)。然而,多因素分析显示HLA I类分子表达与临床结果之间无相关性。
HCRT增加了直肠癌患者的HLA I类分子表达。然而,多因素分析未能显示HLA I类分子表达水平与预后之间存在任何相关性。