PTTG、c-myc及Ki67在胃癌中表达的生物学意义
摘要
目的 探讨垂体肿瘤转化基因(pituitary tumor-transforming gene，PTTG)、c-myc及Ki67在胃癌中表达的生物学意义，为胃癌的早期诊断、判断预后提供理论依据。方法采用免疫组织化学SP法检测40例胃癌组织，15例慢性萎缩性胃炎(其中HP阳性12例，阴性3例)，5例正常胃粘膜组织中PTTG、c-myc及Ki67的表达情况。结果 PTTG及c-myc的阳性反应均主要定位于细胞核，少数胞浆也有着色；Ki67阳性反应定位于细胞核。结果显示：正常胃粘膜、慢性萎缩性胃炎及胃癌中，PTTG阳性表达率分别为0，53.33％，72.50％；c-myc分别为0，60.00％，80.00％；Ki67分别为0，73.33％，95.00％。Nemenyi法两两比较结果显示：胃癌组PTTG的表达强度与正常粘膜组及慢性萎缩性胃炎组间均有极显著性差异(t=3.20，2.73；P=0.0023，0.0085)，而正常粘膜组与慢性萎缩性胃炎组PTTG的表达强度无显著性差异(t=1.34，P=0.1700)；胃癌组c-myc的表达强度与正常粘膜组及慢性萎缩性胃炎组间亦均有显著性差异(t=3.47，2.55；P=0.0010，0.0136)，而正常粘膜组与慢性萎缩性胃炎组间c-myc的表达强度亦无显著性差异(t=1.70，P=0.1000)；胃癌组Ki67的表达强度与正常粘膜组及慢性萎缩性胃炎组间均有显著性差异(t=4.14，2.36；P=0.0011，0.0222)，正常粘膜组与慢性萎缩性胃炎组间Ki67的表达强度亦有显著性差异(t=2.42，P=0.0200)。三者在HP感染的慢性萎缩性胃炎中表达均较强，但因例数少，未行统计学分析。在不同分化和不同临床分期的胃癌中，PTTG的表达均有显著性差异(H=7.160，12.383；P＜0.05，0.05)，c-myc的表达亦均有显著性差异(H=6.315，16.306：P＜0.05，0.001)，Ki67的表达则均有极显著性差异(H=15.551，18.180；P＜0.001，0.001)；PTTG、c-myc及Ki67的表达在淋巴结有转移组与淋巴结无转移组之间，差异均有显著性(H=5.276，5.018，6.369；P＜0.05，0.05，0.05)。癌细胞分化程度越低、临床分期越高、淋巴结有转移，PTTG、c-myc及Ki67的表达均越强。三者的表达与胃癌组织学类型均无关(H=1.222，1.290，0.478：P＞0.05，0.05，0.05)。直线相关分析结果显示：PTTG与Ki67、PTTG与c-myc间的表达强度均呈显著正相关
中文摘要
(r=o.724，0.737;p=0.0一51，0.0375)，e一mye与Ki67之间的表达强度呈极显著
正相关(r=。.893，P=0.0003)。结论1.PTTG及c一myc在正常胃粘膜组织中未见
表达，在慢性萎缩性胃炎中出现表达，胃癌组织中表达最强，说明二者的表达均
与胃癌的发生有关。2.HP阳性的慢性萎缩性胃炎中PTTG、c一myc及Ki67的表
达均强于HP阴性者，提示三者的表达可能与HP感染有关。3.PTTG、c一myc及
Ki67的表达均与胃癌的病理组织学分级、临床分期及淋巴结转移密切相关，提示
三者均可作为判定胃癌恶性程度，评估其侵袭性及转移的分子生物学指标。4.胃
癌组织中PTTG、c一myc及Ki67间的表达强度呈显著正相关，提示三者在胃癌的
发展过程中可能有协同作用。5.联合检测PTTG、c一myc和Ki67在胃癌中的表达
水平，对胃癌的早期诊断、预后判定可能具有重要的参考价值。
Objective To study the biological significance of PTTG (pituitary tumor-transforming gene) c-myc and Ki67 expression in gastric carcinoma (GC). Methods The expression of PTTG c-myc and Ki67 was detected immunohistochemistrically by SP method in 40 cases of GC, 15 cases of chronic atrophic gastritis (CAG) (12 cases with HP infection) and 5 cases of normal gastric mucosa. Results PTTG and c-myc were all mainly expressed in nucleus, and also could be found in cytoplasm. Ki67 expression was located in nucleus. The positive rate of PTTG c-myc and Ki67 in GC, CAG and normal mucosa were 0, 53.33%, 72.5%; 0, 60.00%, 80.00%; 0, 73.33%, 95.00%, respectively. The differences of PTTG expressive intensity between GC and normal mucosa CAG were all obviously significant (t=3.20, 2.73; P=0.0023, 0.0085), but was not significant between normal mucosa and CAG (t=1.34; P=0.1700). It was the same with c-myc expressive intensity between GC and normal mucosa CAG (t=3.47, 2.55; P=0.0010, 0.0136), between normal mucosa and CAG (t=1
.70; P=0.1000). Among the three groups, the expressive intensity of Ki67 were all significant (GC and normal mucosa, GC and CAG, normal mucosa and CAG; t=4.14, 2.36, 2.42; P=0.0011, 0.0222, 0.0200). The expression of PTTG c-myc and Ki67 were all more intensive in CAG with HP infection than that without HP infection, and not done statistics because of few cases. Among histopathological grade and clinical stage groups, the expressive intensity of PTTG were all significantly different (H =7.160, 12.383; P<0.05, 0.05), and was the same with c-myc (H =6.315, 16.306; P<0.05, 0.001), and Ki67 expression (H =15.551, 18.180; P<0.001, 0.001). Between the two groups of lymph node metastasis or not, the expression of PTTG c-myc and Ki67 was also significantly different (H =5.276, 5.018, 6.369; P<0.05, 0.05, 0.05). The expression of PTTG c-myc and Ki67 became strong, along with the decreased histopathological grades, the increased clinical stages and lymph node metastasis. No significances were found between the expressi
on of PTTG
c-myc Ki67 and histological types of GC, respectively (H= 1.222, 1.290, 0.478; P>0.05, 0.05, 0.05). Linear positive correlation was found between the expressive intensity of PTTG and Ki67, PTTG and c-myc (r=0.724,0.737; P=0.018,0.037), c-myc and Ki67 (r=0.893; P=0.0003). Conclusions 1. The expression of PTTG and c-myc can't be seen in normal gastric mucosa, appears in CAG, and is the strongest in GC. It indicates that their expression correlates with the occurrence of GC. 2. The expression of PTTG . c-myc and Ki67 in CAG with HP infection is higher than that without HP infection. It implies that the expression of them may be related to HP infection. 3. The expression of PTTG c-myc and Ki67 is closely correlated with histophatological grade, clinical stage and lymph node metastasis. It may all be served as the molecular biology index of evaluating infitration and metastasis. 4. Positive correlation is found among PTTG c-myc and Ki67, which reveals that they may co-act in the development of GC. 5. United detec
ting the expression of PTTG c-myc and Ki67 may be useful for early diagnosis and eveluating prognosis in GC.
中文摘要
(r=o.724，0.737;p=0.0一51，0.0375)，e一mye与Ki67之间的表达强度呈极显著
正相关(r=。.893，P=0.0003)。结论1.PTTG及c一myc在正常胃粘膜组织中未见
表达，在慢性萎缩性胃炎中出现表达，胃癌组织中表达最强，说明二者的表达均
与胃癌的发生有关。2.HP阳性的慢性萎缩性胃炎中PTTG、c一myc及Ki67的表
达均强于HP阴性者，提示三者的表达可能与HP感染有关。3.PTTG、c一myc及
Ki67的表达均与胃癌的病理组织学分级、临床分期及淋巴结转移密切相关，提示
三者均可作为判定胃癌恶性程度，评估其侵袭性及转移的分子生物学指标。4.胃
癌组织中PTTG、c一myc及Ki67间的表达强度呈显著正相关，提示三者在胃癌的
发展过程中可能有协同作用。5.联合检测PTTG、c一myc和Ki67在胃癌中的表达
水平，对胃癌的早期诊断、预后判定可能具有重要的参考价值。
Objective To study the biological significance of PTTG (pituitary tumor-transforming gene) c-myc and Ki67 expression in gastric carcinoma (GC). Methods The expression of PTTG c-myc and Ki67 was detected immunohistochemistrically by SP method in 40 cases of GC, 15 cases of chronic atrophic gastritis (CAG) (12 cases with HP infection) and 5 cases of normal gastric mucosa. Results PTTG and c-myc were all mainly expressed in nucleus, and also could be found in cytoplasm. Ki67 expression was located in nucleus. The positive rate of PTTG c-myc and Ki67 in GC, CAG and normal mucosa were 0, 53.33%, 72.5%; 0, 60.00%, 80.00%; 0, 73.33%, 95.00%, respectively. The differences of PTTG expressive intensity between GC and normal mucosa CAG were all obviously significant (t=3.20, 2.73; P=0.0023, 0.0085), but was not significant between normal mucosa and CAG (t=1.34; P=0.1700). It was the same with c-myc expressive intensity between GC and normal mucosa CAG (t=3.47, 2.55; P=0.0010, 0.0136), between normal mucosa and CAG (t=1
.70; P=0.1000). Among the three groups, the expressive intensity of Ki67 were all significant (GC and normal mucosa, GC and CAG, normal mucosa and CAG; t=4.14, 2.36, 2.42; P=0.0011, 0.0222, 0.0200). The expression of PTTG c-myc and Ki67 were all more intensive in CAG with HP infection than that without HP infection, and not done statistics because of few cases. Among histopathological grade and clinical stage groups, the expressive intensity of PTTG were all significantly different (H =7.160, 12.383; P<0.05, 0.05), and was the same with c-myc (H =6.315, 16.306; P<0.05, 0.001), and Ki67 expression (H =15.551, 18.180; P<0.001, 0.001). Between the two groups of lymph node metastasis or not, the expression of PTTG c-myc and Ki67 was also significantly different (H =5.276, 5.018, 6.369; P<0.05, 0.05, 0.05). The expression of PTTG c-myc and Ki67 became strong, along with the decreased histopathological grades, the increased clinical stages and lymph node metastasis. No significances were found between the expressi
on of PTTG
c-myc Ki67 and histological types of GC, respectively (H= 1.222, 1.290, 0.478; P>0.05, 0.05, 0.05). Linear positive correlation was found between the expressive intensity of PTTG and Ki67, PTTG and c-myc (r=0.724,0.737; P=0.018,0.037), c-myc and Ki67 (r=0.893; P=0.0003). Conclusions 1. The expression of PTTG and c-myc can't be seen in normal gastric mucosa, appears in CAG, and is the strongest in GC. It indicates that their expression correlates with the occurrence of GC. 2. The expression of PTTG . c-myc and Ki67 in CAG with HP infection is higher than that without HP infection. It implies that the expression of them may be related to HP infection. 3. The expression of PTTG c-myc and Ki67 is closely correlated with histophatological grade, clinical stage and lymph node metastasis. It may all be served as the molecular biology index of evaluating infitration and metastasis. 4. Positive correlation is found among PTTG c-myc and Ki67, which reveals that they may co-act in the development of GC. 5. United detec
ting the expression of PTTG c-myc and Ki67 may be useful for early diagnosis and eveluating prognosis in GC.
引文
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6 Sacz C, Japon MA, Ramos-Morales F, et al. hpttg is over-expressed in pituitary adenomas and other pituitary epithelial neoplaisas [J]. Oncogcnc, 1999, 18: 5473-5476
7 Yamada M, Assnuma K, Yagihashi A, et al. Human pituitary tumor transforming genel(hpTTG1) in gastric mucosal tissues. Am-J-Gastroentera, 2001, 96(4): 1313-1314
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49 Loke SL, Murakami T, Kawasaki, et al. J cellular Physiol, 1987,133:579-584
50 Ramos-Morales F, Dominguez A, Romero F, et al. Cell cycle regulated expression and phosphorylation of hpttg proto-oncoge be product.Oncoge be, 2000, 19(3): 403-409
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2 Zhang X, Horwitz GA, Prezant TR, et al. Structure, expression, and function of human pituitary tumor-transforming gone (hPTTG) [J]. Mol Endocrinol, 1999, 13: 156-166
3 Heaney AP, Singson R, McCabe CJ, et al Expression of pituitary tumor-transforming geae in colorectal tumor[J].Lancet, 2000, 355:716-719
4 Kakar SS. Molecular cloning, genomic organization, and identification of the promoter for the human pituitary tumor-transforming gene (hPTTG)[J]. Gene, 1999, 240:317-324
5 Zhang X, Horwitz GA, Hcaney AP, et al. Pituitary tumor-transforming gone (PTTG) expression in pituitary adenomas [J]. J Clin Endocrinol Metab, 1999, 84:761-767
6 Sacz C, Japon MA, Ramos-Morales F, et al. hpttg is over-expressed in pituitary adenomas and other pituitary epithelial neoplaisas [J]. Oncogcnc, 1999, 18: 5473-5476
7 Yamada M, Assnuma K, Yagihashi A, et al. Human pituitary tumor transforming genel(hpTTG1) in gastric mucosal tissues. Am-J-Gastroentera, 2001, 96(4): 1313-1314
8 Kretzner L, Blackwood E, Eisenman R, et al. Myc and Max proteins possess distinct transcription activities. Nature. 1992, 359 (6394): 426-429
9 彭解人，曾韵洁，许耀东，等。P16与c-myc在喉鳞状细胞癌中的表达意义。临床耳鼻喉杂志，1997，5(1)：22—24
10 丁强，张元芳，孙逊，等。睾丸肿瘤组织中C-myc基因扩增和表达及其临床意义．中华泌尿外科杂志，1996，17：497—499
11 刘平果，钟德|WU|，杨竹林，等．原发性肝癌组织中c-myc癌基因、Ki67抗原的表达与意义。中华肝胆外科杂志，1999，5(1)：32—34
12 方|YAN|，黄必军，梁启万，等。应用间期荧光原位杂交技术检测原发性肝细胞癌c-myc癌基因扩增的临床意义。中华病理学杂志，2001，30(3)：180-182
13 李允模，尹香花，安昌善，等。肺癌组织中癌基因ras和c-myc蛋白产物
的免疫组织化学研究。延边大学医学学报，1999，22(1)：42-45
14 祁晓莉，戴洁，韩兰唐，等．胃原发癌和淋巴结转移癌细胞中bc1-2和c-myc基因蛋白表达的研究。实用癌症杂志，1999，14(4)：253-255
15 Chien W, Pei L. A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product [J]. J Biol Chem, 2000, 275:19422-19427
16 Pei L. Activation of mitogen-activated protein kinase cascade regulatrs pituitary tumor-transforming gene transsactivation function[J]. J Biol Chem, 2000, 275:31191-31198
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