Department of Breast Oncology and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
PLoS One. 2012;7(1):e31181. doi: 10.1371/journal.pone.0031181. Epub 2012 Jan 27.
Development of tailored treatment based on immunohistochemical profiles (IPs) of tumors for cancers of unknown primary is needed.
METHODOLOGY/PRINCIPAL FINDINGS: We developed an algorithm based on primary known adenocarcinoma for testing sensitivity and specificity. Formalin-fixed paraffin-embedded tissue samples from 71 patients of unfavorable subsets of unknown primary adenocarcinoma were obtained. We examined 15 molecular markers using the algorithm incorporating these IPs and classified the tumours into 9 subsets based on the primary tumour site. The sensitivity and specificity of this algorithm were 80.3% and 97.6%, respectively. Apparent primary sites were lung in 17 patients, digestive organs in 13, gynecological organs in 9, prostate in 7, liver or kidney in 6, breast in 4, urothelial organ in 2, biliary tract and pancreatic profile in none, and unclassified in 13. The response rate to chemotherapy was highest for the gynecological IPs. Patients with gynecological or lung cancer IPs had longer median progression-free survival than those with others: 11.2 months for gynecological IPs (p<0.001) and 6.8 months for lung IPs (p = 0.05). Lung, digestive, prostate, and gynecological profiles were associated with significantly longer median survival time than the other profiles. Multivariate analysis confirmed that the IPs were independent prognostic factors for survival.
CONCLUSIONS/SIGNIFICANCE: The IPs identified in this study can be used to further stratify patient prognosis for unfavorable subsets of unknown primary adenocarcinoma.
需要根据肿瘤的免疫组织化学特征（IP）为原发灶不明的癌症开发定制化的治疗方法。
方法/主要发现：我们开发了一种基于已知原发腺癌的算法，用于测试其敏感性和特异性。从 71 例不利亚组的原发灶不明腺癌患者中获得了福尔马林固定石蜡包埋组织样本。我们使用该算法检测了 15 种分子标志物，并根据原发肿瘤部位将肿瘤分为 9 个亚组。该算法的敏感性和特异性分别为 80.3%和 97.6%。17 例患者的原发灶为肺部，13 例为消化系统，9 例为妇科，7 例为前列腺，6 例为肝脏或肾脏，4 例为乳腺，2 例为尿路上皮器官，胆道和胰腺均无，13 例为未分类。妇科 IP 患者的化疗反应率最高。具有妇科或肺癌 IP 的患者无进展生存期长于其他患者：妇科 IP 为 11.2 个月（p<0.001），肺癌 IP 为 6.8 个月（p=0.05）。肺、消化系统、前列腺和妇科的 IP 与中位生存时间显著延长相关。多变量分析证实，IP 是生存的独立预后因素。
结论/意义：本研究中鉴定的 IP 可用于进一步分层原发灶不明的不利亚组腺癌患者的预后。
