以免疫組織化學法分析子宮頸腫瘤CIN1及CIN3中的CCNB1,Ras, TMOD3,ＮUDT9及PLSCR4蛋白

Immunohistochemical analysis of CCNB1,Ras,TMOD3,NUDT9 and PLSCR4 proteins in CIN1 and CIN3 cervical neoplasm.

張森鈴(Shen-ling Chang)

指導教授 ： 陳凌雲

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2007年)

https://doi.org/10.6834/CSMU.2007.00025

摘要

中文摘要
子宮頸癌是目前台灣地區女性癌症死因的第六位，死亡率約為每十萬名人口7.0例，僅次於肺癌、肝癌、直腸結腸癌、乳癌、胃癌，更是佔全球女性癌症的第二位。本研究之目的是分析在正常和子宮頸
上皮內腫瘤(cervical intraepithelial neoplasm; CIN)的不同蛋白表達情形及其之間的相關性，探討以免疫組織化學(Immunohistochemical
stain)做為子宮頸前期癌的特異性標的物的可能性，以期尋找新的子宮頸前期癌篩檢方法。在研究中針對12個正常或鱗狀上皮化生(Normal or Squamous metaplasia)、28個輕度異形病變(CIN1 & HPV; LSIL)及23個原位癌(CIN3; HSIL)之個案以CCNB1、Ras、TMOD3、NUDT9及PLSCR4的抗體以IHC方法了解不同的蛋白在子宮頸腫瘤中的表現量並做比較分析，由實驗得知TMOD3在正常或鱗狀上皮化生的子宮頸組織中其蛋白表現量很多，佔100% (12/12)，輕度異形病變(CIN1; LSIL) 佔89.0% (25/28)，原位癌(CIN3; HSIL) 佔48.0% (11/23)；正常與原位癌之差異性比較是有意義的(P < 0.05)。PLSCR4的蛋白表現量在正常與原位癌組織亦是有差異性(P < 0.05)。在輕度異形病變(CIN1)之28個案加以追蹤探討，得知PLSCR4-exon 4 及PLSCR4-exon 6在IHC stain呈現陰性反應的個案，有回診做抹片檢查為正常者有100% (p=0.003)，若繼續追蹤更久及更多案例仍呈現相同的結果，則此PLSCR4在臨床應用將是一件有貢獻的重大發現。

關鍵字

子宮頸前期癌

並列摘要

Abstract
Cervical cancer is the sixth cause of cancer death in Taiwanese women at present, second only to lung cancer, liver cancer, rectum colon cancer, breast cancer and stomach cancer, it also accounts for the second cause of women’s cancer in the world. The purpose of the present study is to evaluate the expression of different proteins in the normal uterine cervix or cervical intraepithelial neoplasm and try to find a marker for intraepithelial neoplasm detection or prognosis prediction.We collected cervical specimens from 12 women with normal cervix histology, 28 diagonosed as mild dysplasia (CIN I) and 23 cases diagnosed as carcinoma in situ (CIS) and performed immunohistochemistry staining (IHC) with CCNB1, Ras, TMOD3, NUDT9, PLSCR4-exon4 and PLSCR4-exon6 antibodies，The IHC results showed the TMOD3 was positive in 100% (12/12) of normal cervical specimen, 89.0% (12/12) and 48.0%(11/23) cervical intraepithelial neoplasm grade I (CINI) and carcinoma in situ (CIS) specimens respectively, The difference of positive rates between normal cervical tissue and CIS was statistically significant . The difference of PLSCR4 exon 4 and exon 6 positive rate between normal cervical tissue and CIS was also statistically significant. (p<0.05) We followed up those patients with CINI and tried to correlate the initially PLSCR4 IHC results and the followed–up Pap smear. Suprisingly we find those patients with negative IHC results for both PLSCR4 exon4 and exon 6 all (2/2) showed disease free in the followd- up Pap smear, but 57.1% (8/14) patients with postitive IHC for either PLSCR4 exon 4 or exon 6 still showed residual CIN 1. These finding suggest PLSCR4 may be used as a biochemical marker to predict the prognosis of CIN 1, though more cases and longer followed-up are needed.

並列關鍵字

CCNB1 ； Ras ； TMOD3 ； NUDT9 ； PLSCR4

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