Deveci M Salih, Deveci Güzin
Department of Pathology, Gülhane Military Medical Academy, Etlik, Ankara, Turkey.
Gastric Cancer. 2007;10(2):112-6. doi: 10.1007/s10120-007-0418-7. Epub 2007 Jun 25.
MK-1, the target molecule of FU-MK-1, is encoded by the GA733-2 gene, which is currently being used as a target in clinical trials for gastric, intestinal and biliary cancer treatment with monoclonal antibodies. Also of interest is p53, a protein that has been intensively investigated in relation to particular types of tumors, patterns of metastases, tumor stage, and prognosis.
The expression of p53 protein and MK-1 antigen was investigated in specimens from 42 patients with gastric carcinoma. The specimens were stained by the avidin-biotin peroxidase technique for immunohistochemical examination.
MK-1 was positive in 21 (50%) of the 42 cases. MK-1 expression was more frequent in cardia tumors (71%), in large (>3 cm) tumors (60%-64%), and in specimens from patients with more than five metastatic lymph nodes (69%). p53 expression was present in 20 (48%) of the 42 cases. Of these 20 patients, 15 (52%) had tubular adenocarcinoma (TA) and 5 (38%) had signet ring cell carcinoma. p53 expression was more frequent in the tumors of male patients (55% vs 27%); in poorly differentiated TAs (60% vs 47% in well-to-moderately differentiated TAs); in smaller tumors (< or = 3 cm, 72% vs 43%-50% in larger tumors); in patients with a prominent inflammatory response (61% vs 21%; P < 0.02); and in patients with lymphatic vessel invasion (77% vs 34%; P < 0.02). However, p53 expression was less frequent in the presence of more than five metastatic lymph nodes (23% vs 60% for five or fewer nodes; P < 0.05). Most patients with p53- and MK-1-positive gastric carcinomas and those more than five metastatic lymph nodes had a poor prognosis.
The study found that the expression of both p53 and MK-1 was frequent in aggressive gastric carcinomas; however, extensive lymph node involvement (more than five nodes) was the only significant factor related to overall survival.
FU-MK-1的靶分子MK-1由GA733-2基因编码，目前该基因正被用作胃癌、肠癌和胆管癌单克隆抗体治疗临床试验的靶点。同样受关注的是p53，一种已针对特定类型肿瘤、转移模式、肿瘤分期和预后进行深入研究的蛋白质。
对42例胃癌患者的标本进行p53蛋白和MK-1抗原表达研究。标本采用抗生物素蛋白-生物素过氧化物酶技术染色进行免疫组化检查。
42例病例中21例（50%）MK-1呈阳性。MK-1在贲门肿瘤（71%）、大肿瘤（>3 cm，60%-64%）以及有5个以上转移淋巴结患者的标本中（69%）表达更为频繁。42例病例中20例（48%）存在p53表达。在这20例患者中，15例（52%）为管状腺癌（TA），5例（38%）为印戒细胞癌。p53在男性患者肿瘤中表达更为频繁（55%对27%）；在低分化TA中（60%对高-中分化TA中的47%）；在较小肿瘤（≤3 cm，72%对较大肿瘤中的43%-50%）；在有显著炎症反应的患者中（61%对21%；P<0.02）；以及在有淋巴管侵犯的患者中（77%对34%；P<0.02）。然而，在有5个以上转移淋巴结的情况下，p53表达较少见（5个或更少淋巴结时为60%，而5个以上淋巴结时为23%；P<0.05）。大多数p53和MK-1阳性的胃癌患者以及有5个以上转移淋巴结的患者预后较差。
该研究发现p53和MK-1在侵袭性胃癌中表达均较为频繁；然而，广泛的淋巴结受累（超过5个淋巴结）是与总生存期相关的唯一重要因素。
