子宫内膜癌免疫组织化学及临床病理特征研究
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摘要
目的：探讨应用CK7(细胞角蛋白7)、CK20(细胞角蛋白20)、vimentin(波形蛋白)、CA125、TAG-72(肿瘤协同糖蛋白—72)、S-100蛋白、Leu-M_1和cyclinE(细胞周期素E)鉴别诊断子宫内膜癌不同病理类型的可能性；同时对比研究Ⅰ型(雌激素依赖型)和Ⅱ型(非雌激素依赖型)子宫内膜癌在临床病理特征方面的差异。
方法：本实验选择1994年至2002年武汉大学中南医院病理科存档的85例子宫内膜癌病例，包括65例内膜样腺癌，9例浆液性腺癌，2例透明细胞癌，4例粘液性腺癌及5例鳞状细胞癌。同时选择30例卵巢上皮性肿瘤(10例内膜样腺癌；12例浆液性腺癌；5例透明细胞癌及3例粘液性腺癌)和10例肾脏透明细胞癌作为对比研究。SP免疫组化法检测CK7、CK20、vimentin、CA125、TAG-72、S-100蛋白、Leu-M_1和cyclinE在肿瘤中的表达。
结果：(1)除鳞状细胞癌外，所有子宫内膜癌均呈CK7(+)／CK20(-)表达。vimentin在子宫内膜样腺癌中的表达高于其它类型(P＜0.01)。CA125的表达在妇科粘液性肿瘤与非粘液性肿瘤间有极显著差异(P＜0.01)。4／9(44.44％)浆液性癌中局部癌细胞团表达S-100。cyclinE在子宫内膜和卵巢透明细胞癌中的表达较其它类型要高(P＜0.01)。TAG-72及Leu-M_1的表达在子宫内膜癌和卵巢癌各种病理类型中无明显差别。子宫内膜鳞状细胞癌的免疫表型较其它病理类型有明显不同。免疫组织化学显示卵巢上皮性肿瘤的大多数免疫表型与子宫内膜癌相似，但2例卵巢粘液性腺癌CK20为阳性表达。(2)免疫组织化学结果显示，CK7、CA125及cyclinE在妇科透明细胞癌中有表达，但在肾脏透明细胞癌无表达(P＜0.05或P＜0.01)。(3)Ⅰ型子宫内膜癌占74.12％(63／85)，Ⅱ型占25.88％(22／85)。Ⅱ型以绝经后患者多见(P＜0.05)。具有较高恶性程度的非内膜样腺癌(包括浆液性腺癌、透明细胞癌)在Ⅱ型中占40.91％(9／22)，在Ⅰ型中仅占3.17％(2／63)，差异具有统计学意义(P＜0.05)。Ⅱ型子宫内膜癌的分级以中、低分化多见，深肌层浸润例数明显高于Ⅰ型(P均＜0.01)，手术-病理Ⅲ、Ⅳ期的比率较Ⅰ型亦有显著增加(P＜0.05)。
结论：(1)子宫内膜鳞状细胞癌的免疫表型与其它亚型子宫内膜癌有明显不同。
子宫内膜样腺癌、浆液性腺癌、粘液性腺癌及透明细胞癌均显示CK7(+)/C K20(一)表达
特征。(2)在子宫内膜癌中，vimentin(+)、CA125C)及eyelinE(+)表达分别在子宫内膜
样腺癌、粘液性腺癌及透明细胞癌的诊断及鉴别诊断中有意义。(3)卵巢子宫内膜样
腺癌、浆液性腺癌、粘液性腺癌及透明细胞癌与相应子宫内膜癌病理亚型在大多数免
疫标记物的表达上具有相似性。(4) CK7、CA125及cyclinE是鉴别妇科透明细胞癌及
肾脏透明细胞癌的有用指标。cyclinE的高表达是起源于苗勒氏管的透明细胞癌的一个
重要特征。(5)与工型子宫内膜癌相比，11型多为浆液性腺癌和透明细胞癌。且肿瘤
多分级高，肌层浸润深，手术一病理分期晚，因而预后差。
Objective: To investigate the possibility of distinguishing between the different kinds of endometrial carcinoma by using a panel of immunohistochemical stains, which included cytokeratins 7 and 20(CK7 and CK20), vimentin, CA125, tumor-associated glycoprotein (TAG-72), S-100, Leu-Mi and cyclinE. We also investigate the difference in the clinicopathological characteristics of type I (estrogen-dependent) and type II (estrogen-independent) of endometrial carcinoma.
Methods: 85 cases stored in Department of Pathology, Zhongnan Hospital, Wuhan University between 1994 and 2002 were available for the study including 65 cases of endometrioid adenocarcinoma, 9 cases of serous cacinoma, 2 cases of clear cell carcinoma, 4 cases of mucinous carcinoma and 5 cases of squamous carcinoma. For comparison, 30 cases of epithelial ovarian tumors(10 cases of endometrioid adenocarcinoma, 12 cases of serous cacinoma, 5 cases of clear cell carcinoma, 3 cases of mucinous carcinoma) and 10 cases of renal clear cell carcinoma were also studied. The expressions of CK7, CK 20, vimentin, CA125, TAG-72, S-100, Leu-Mi and cyclinE were detected by means of SP immunohistochemical method.
Resutls: (1) Except squamous carcinoma , all the endometrial carcinoma were CK7(+) /CK20(-). Endometrioid adenocarcinoma were mostly vimentin(+), higher than other tissue types (P<0.01) .There was a significant difference in the expression of CA125 between mucinous tumors and non-mucinous tumors(P<0.01) .Four of nine(44.44%) serous carcinomas showed focal staining for S-100 protein. CyclinE expression tended to be more frequent in clear cell carcinomas of the endometrium and ovary than in other classes of gynecologic cancers (P<0.01) .The expressions of Tag-72 and Leu-Mi had no significant difference in different kinds of endometrial tumors and ovarian tumors. Squamous carcinoma of the endometrium showed different immunophenotype from the other types. Most of immunophenotypes in the endometrial carcinomas were similar to the ovarian cancer, but two cases of mucinous carcinoma of ovary showed CK20(+). (2)
Immunohistochemistry revealed a higher level of expression of CK7, CA125 and cyclinE in gynecologic clear cell carcinoma, but not in clear cell carcinoma of renal origin(P<0.05 or P<0.01). (3) The incidence in type I and type II were 74.12%(63/85) and 25.88%(22/85) respectively, The rate of postmenopause patients in type II was significanctly higher than that in type I (P<0.05).There were more virulent types of nonendometrioid carcinoma(serous carcinoma, clear cell carcinoma) in type II as compared with type I ( P<0.01 ). The rate of high grade(grade 2,3) ,deep myometrial invasion and surgical-pathological staging III or IV in type II were higher than those in type I respectively(P<0.05 orP<0.01 ).
Conclusions: (l)The immunophenotype of endometrial squamous carcinoma are obviously different to other kinds of endometrial carcinomas. Endometrioid carcinoma, serous carcinoma, mucinous carcinoma and clear cell carcinoma of the endometrium show CK7(+)/CK20(-). (2)In endometrial cancers, vimentin(+), CA125(-) and cyclinE(+) may be useful in the differential diagnosis of the endometrioid carcinoma, mucinous carcinoma and clear cell carcinoma. (3) Most of immunophenotypes in the endometrial carcinomas were similar to the ovarian cancer. (4)Using CK7, CA125 and cyclinE can be distinguished clear cell carcinoma of kidney and gynecology. Immunohistochemistry activity of cyclinE is a property of clear cell carcinoma of M llerian origin.(5)For comparison with type I endometrial carcinoma, type II has more virulent types of nonendometrioid carcinoma(serous carcinoma, clear cell carcinoma) and is a more malignant type with high grade, deep myometrial invasion and late surgical-pathological stage. Therefore, the progn
osis of type II is worse than of type I .
方法：本实验选择1994年至2002年武汉大学中南医院病理科存档的85例子宫内膜癌病例，包括65例内膜样腺癌，9例浆液性腺癌，2例透明细胞癌，4例粘液性腺癌及5例鳞状细胞癌。同时选择30例卵巢上皮性肿瘤(10例内膜样腺癌；12例浆液性腺癌；5例透明细胞癌及3例粘液性腺癌)和10例肾脏透明细胞癌作为对比研究。SP免疫组化法检测CK7、CK20、vimentin、CA125、TAG-72、S-100蛋白、Leu-M_1和cyclinE在肿瘤中的表达。
结果：(1)除鳞状细胞癌外，所有子宫内膜癌均呈CK7(+)／CK20(-)表达。vimentin在子宫内膜样腺癌中的表达高于其它类型(P＜0.01)。CA125的表达在妇科粘液性肿瘤与非粘液性肿瘤间有极显著差异(P＜0.01)。4／9(44.44％)浆液性癌中局部癌细胞团表达S-100。cyclinE在子宫内膜和卵巢透明细胞癌中的表达较其它类型要高(P＜0.01)。TAG-72及Leu-M_1的表达在子宫内膜癌和卵巢癌各种病理类型中无明显差别。子宫内膜鳞状细胞癌的免疫表型较其它病理类型有明显不同。免疫组织化学显示卵巢上皮性肿瘤的大多数免疫表型与子宫内膜癌相似，但2例卵巢粘液性腺癌CK20为阳性表达。(2)免疫组织化学结果显示，CK7、CA125及cyclinE在妇科透明细胞癌中有表达，但在肾脏透明细胞癌无表达(P＜0.05或P＜0.01)。(3)Ⅰ型子宫内膜癌占74.12％(63／85)，Ⅱ型占25.88％(22／85)。Ⅱ型以绝经后患者多见(P＜0.05)。具有较高恶性程度的非内膜样腺癌(包括浆液性腺癌、透明细胞癌)在Ⅱ型中占40.91％(9／22)，在Ⅰ型中仅占3.17％(2／63)，差异具有统计学意义(P＜0.05)。Ⅱ型子宫内膜癌的分级以中、低分化多见，深肌层浸润例数明显高于Ⅰ型(P均＜0.01)，手术-病理Ⅲ、Ⅳ期的比率较Ⅰ型亦有显著增加(P＜0.05)。
结论：(1)子宫内膜鳞状细胞癌的免疫表型与其它亚型子宫内膜癌有明显不同。
子宫内膜样腺癌、浆液性腺癌、粘液性腺癌及透明细胞癌均显示CK7(+)/C K20(一)表达
特征。(2)在子宫内膜癌中，vimentin(+)、CA125C)及eyelinE(+)表达分别在子宫内膜
样腺癌、粘液性腺癌及透明细胞癌的诊断及鉴别诊断中有意义。(3)卵巢子宫内膜样
腺癌、浆液性腺癌、粘液性腺癌及透明细胞癌与相应子宫内膜癌病理亚型在大多数免
疫标记物的表达上具有相似性。(4) CK7、CA125及cyclinE是鉴别妇科透明细胞癌及
肾脏透明细胞癌的有用指标。cyclinE的高表达是起源于苗勒氏管的透明细胞癌的一个
重要特征。(5)与工型子宫内膜癌相比，11型多为浆液性腺癌和透明细胞癌。且肿瘤
多分级高，肌层浸润深，手术一病理分期晚，因而预后差。
Objective: To investigate the possibility of distinguishing between the different kinds of endometrial carcinoma by using a panel of immunohistochemical stains, which included cytokeratins 7 and 20(CK7 and CK20), vimentin, CA125, tumor-associated glycoprotein (TAG-72), S-100, Leu-Mi and cyclinE. We also investigate the difference in the clinicopathological characteristics of type I (estrogen-dependent) and type II (estrogen-independent) of endometrial carcinoma.
Methods: 85 cases stored in Department of Pathology, Zhongnan Hospital, Wuhan University between 1994 and 2002 were available for the study including 65 cases of endometrioid adenocarcinoma, 9 cases of serous cacinoma, 2 cases of clear cell carcinoma, 4 cases of mucinous carcinoma and 5 cases of squamous carcinoma. For comparison, 30 cases of epithelial ovarian tumors(10 cases of endometrioid adenocarcinoma, 12 cases of serous cacinoma, 5 cases of clear cell carcinoma, 3 cases of mucinous carcinoma) and 10 cases of renal clear cell carcinoma were also studied. The expressions of CK7, CK 20, vimentin, CA125, TAG-72, S-100, Leu-Mi and cyclinE were detected by means of SP immunohistochemical method.
Resutls: (1) Except squamous carcinoma , all the endometrial carcinoma were CK7(+) /CK20(-). Endometrioid adenocarcinoma were mostly vimentin(+), higher than other tissue types (P<0.01) .There was a significant difference in the expression of CA125 between mucinous tumors and non-mucinous tumors(P<0.01) .Four of nine(44.44%) serous carcinomas showed focal staining for S-100 protein. CyclinE expression tended to be more frequent in clear cell carcinomas of the endometrium and ovary than in other classes of gynecologic cancers (P<0.01) .The expressions of Tag-72 and Leu-Mi had no significant difference in different kinds of endometrial tumors and ovarian tumors. Squamous carcinoma of the endometrium showed different immunophenotype from the other types. Most of immunophenotypes in the endometrial carcinomas were similar to the ovarian cancer, but two cases of mucinous carcinoma of ovary showed CK20(+). (2)
Immunohistochemistry revealed a higher level of expression of CK7, CA125 and cyclinE in gynecologic clear cell carcinoma, but not in clear cell carcinoma of renal origin(P<0.05 or P<0.01). (3) The incidence in type I and type II were 74.12%(63/85) and 25.88%(22/85) respectively, The rate of postmenopause patients in type II was significanctly higher than that in type I (P<0.05).There were more virulent types of nonendometrioid carcinoma(serous carcinoma, clear cell carcinoma) in type II as compared with type I ( P<0.01 ). The rate of high grade(grade 2,3) ,deep myometrial invasion and surgical-pathological staging III or IV in type II were higher than those in type I respectively(P<0.05 orP<0.01 ).
Conclusions: (l)The immunophenotype of endometrial squamous carcinoma are obviously different to other kinds of endometrial carcinomas. Endometrioid carcinoma, serous carcinoma, mucinous carcinoma and clear cell carcinoma of the endometrium show CK7(+)/CK20(-). (2)In endometrial cancers, vimentin(+), CA125(-) and cyclinE(+) may be useful in the differential diagnosis of the endometrioid carcinoma, mucinous carcinoma and clear cell carcinoma. (3) Most of immunophenotypes in the endometrial carcinomas were similar to the ovarian cancer. (4)Using CK7, CA125 and cyclinE can be distinguished clear cell carcinoma of kidney and gynecology. Immunohistochemistry activity of cyclinE is a property of clear cell carcinoma of M llerian origin.(5)For comparison with type I endometrial carcinoma, type II has more virulent types of nonendometrioid carcinoma(serous carcinoma, clear cell carcinoma) and is a more malignant type with high grade, deep myometrial invasion and late surgical-pathological stage. Therefore, the progn
osis of type II is worse than of type I .
引文
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2. Scully RE, Bonfiglio TA, Kurman RJ, et al. Histological Typing of Female Genital Tract Tumours (WHO) . Springer Verlag.1994, Second Edition: 14-18
3. 李璞主编．医用生物学(高等医药学院教材)．第四版．人民卫生出版社，1994：44-45
4. Roland Einarsson, Phd. Vivian Barak Phd. TPS-A cytokeratin serum tumor marker for the effective therapy control of cancer patients with focus on breast cancers. J Clin Ligand Assay, 1999,22(4): 348-351
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8. Zemer R, Fishman A, Klein A, et al. Detection of micrometastasis by cytokeratin-20 (reversen transcription polymerase chain reaction) in lymph nodes of patients with endometrial cancer. Gynecol oncol, 2000, 77(3):399-404
9. Traub P, Nelson WJ. Interaction of the intermediate filament protein vimentin with ribosomal subunits and ribosomal RNA in vitro. Mol Biol Rep,1982,8(4): 239-247
10. Leader M, CoLLins M, patel J, et al. Vimentin: an evaluation of its role as a tumour marker. Histopathol,1987,11(1): 63-72
11. Domagala W, Striker G, Szadowska A, et al. P53 protein and vimentin in invasive ductal NOS breast carcinoma relationship with survival and sites of metastases. Eur J Cancer. 1994,30A (10): 1527-1534
12. Raymond WA, Leong AS. Vimentin-A new prognostic parameter in breast carcinoma ? J Pathol,1989,158(2): 107-114
13. Gown AM,Vogel AM. Monoclonal antibodies to human intermediate filament proteins Ⅲ.Analysis of tumors. Am J Clin Pathol, 1985,85(4):413-424
14. McNutt MA, Bolen JW, Gown AM, et al. Coexpression of intermediate filaments in human epithelial neoplasms. Ultrastruct Pathol, 1985, 9(1-2):31-43
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2. Scully RE, Bonfiglio TA, Kurman RJ, et al. Histological Typing of Female Genital Tract Tumours (WHO) . Springer Verlag.1994, Second Edition: 14-18
3. 李璞主编．医用生物学(高等医药学院教材)．第四版．人民卫生出版社，1994：44-45
4. Roland Einarsson, Phd. Vivian Barak Phd. TPS-A cytokeratin serum tumor marker for the effective therapy control of cancer patients with focus on breast cancers. J Clin Ligand Assay, 1999,22(4): 348-351
5. Einarsson R. Cytokeratins as tumor markers-molecular and clinical data with focus on TPS. J Tumor Marker Oncol, 2000, 15(3):163-172
6. Berezowski K, Stastnv PF, Kurrstem MJ. Cytokertin 7 and 20 and carcinoembryome antigen in ovarian and colonic carcinoma. Mod Pathol, 1996, 9(4):426-429
7. Wang NP, Zee S, Zarbo RJ, et al. Coordianate expression of cytokertins 7 and 20 defines unique subsets of carcinoma. Appl Immunohistochem, 1993, 3 (2):99-107
8. Zemer R, Fishman A, Klein A, et al. Detection of micrometastasis by cytokeratin-20 (reversen transcription polymerase chain reaction) in lymph nodes of patients with endometrial cancer. Gynecol oncol, 2000, 77(3):399-404
9. Traub P, Nelson WJ. Interaction of the intermediate filament protein vimentin with ribosomal subunits and ribosomal RNA in vitro. Mol Biol Rep,1982,8(4): 239-247
10. Leader M, CoLLins M, patel J, et al. Vimentin: an evaluation of its role as a tumour marker. Histopathol,1987,11(1): 63-72
11. Domagala W, Striker G, Szadowska A, et al. P53 protein and vimentin in invasive ductal NOS breast carcinoma relationship with survival and sites of metastases. Eur J Cancer. 1994,30A (10): 1527-1534
12. Raymond WA, Leong AS. Vimentin-A new prognostic parameter in breast carcinoma ? J Pathol,1989,158(2): 107-114
13. Gown AM,Vogel AM. Monoclonal antibodies to human intermediate filament proteins Ⅲ.Analysis of tumors. Am J Clin Pathol, 1985,85(4):413-424
14. McNutt MA, Bolen JW, Gown AM, et al. Coexpression of intermediate filaments in human epithelial neoplasms. Ultrastruct Pathol, 1985, 9(1-2):31-43
15. Gould VE. The coexpression of distinct classes of intermediate filaments in human neoplasms[Editorial]. Arch Pathol Lab Med, 1985,109(11):984-985
16. Norwitz ER, Femandez-Shaw, Barlow DH, et al. Expression of intermediate filament in endometrial glands changes with the onset of pregnancy and in endometriosis. Hum Reprod, 1991,6(10): 1470-1473
17. 17.N.Papadopoulos, A.Kotini, Cheva, et al. Immunhistochemical expression of vimentin and secretory component antigens in endometrial hyperplasia and neoplasia. Eur J Gynaee Oncol ,2002, 239(5):411-414
18. schbartz PE, Taylor KJ. Is early dection ovarian cancer possible ? Ann Med ,1995,27 (5): 519-523
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