• 大連醫(yī)科大學附屬第二醫(yī)院(暨大連醫(yī)科大學附屬腫瘤醫(yī)院)普通外科(遼寧大連 116023);

目的  檢測細胞角蛋白5/6 (CK5/6)和Ki-67在乳腺癌組織中的表達情況,并探討其臨床意義。
方法  應(yīng)用免疫組織化學方法檢測162例乳腺癌患者中CK5/6與Ki-67的表達情況,分析CK5/6與Ki-67表達的相關(guān)性以及其與乳腺癌患者的臨床病理資料的關(guān)系。
結(jié)果  162例乳腺癌患者中三陰性乳腺癌(ER、PR及Her陰性)共12例。CK5/6和Ki-67在162例乳腺癌患者中的表達陽性率分別為30.9% (50/162)及65.4% (106/162),其在三陰性乳腺癌患者中的表達陽性率均明顯高于其在非三陰性乳腺癌患者中的表達〔CK5/6:75.0% (9/12)比27.3% (41/150),χ2=11.837,P=0.001;Ki-67:100% (12/12)比62.7% (94/150),χ2=6.847,P=0.009〕。CK5/6與Ki-67在乳腺癌中的表達均與患者年齡無關(guān)(P>0.05),均與組織學分級有關(guān)(P<0.05)。CK5/6在乳腺癌組織中的表達與乳腺腫瘤大小和淋巴結(jié)轉(zhuǎn)移無關(guān)(P>0.05),而Ki-67在乳腺癌組織中的表達卻與其有關(guān)(P<0.05)。CK5/6與Ki-67在乳腺癌組織中的表達呈顯著正相關(guān)(rs=0.271,P=0.000)。Ki-67在乳腺癌組織中的表達為(++)和(+++)的病例共64例,其中CK5/6陽性率為43.8%(28/64),明顯高于Ki-67在乳腺癌組織中表達為(-)和(+)時的22.4%
(22/98),差異有統(tǒng)計學意義(χ2=8.233,P=0.004)。CK5/6和Ki-67在乳腺癌組織中的陽性表達均與ER、PR表達呈顯著負相關(guān)(CK5/6與ER:rs=-0.446,P=0.000;CK5/6與PR:rs=-0.370,P=0.000;Ki-67與ER:rs=-0.518,P=0.000;Ki-67與PR:rs=-0.515,P=0.000),二者均與Her-2的陰性表達無明顯相關(guān)性(CK5/6與Her-2:rs=-0.105,P=0.183;Ki-67與Her-2:rs=0.068,P=0.393)。
結(jié)論  CK5/6與Ki-67聯(lián)合檢測可以從來源及發(fā)展上評估乳腺癌疾病的基本規(guī)律,為乳腺癌術(shù)后化療提供指導(dǎo)。

引用本文: 李紀男,馬振海,徐景超,趙永福. 聯(lián)合檢測乳腺癌組織中CK5/6、Ki-67表達的臨床意義△. 中國普外基礎(chǔ)與臨床雜志, 2013, 20(11): 1245-1249. doi: 復(fù)制

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012[J]. CA Cancer J Clin, 2012, 62(1):10-29.
2. Campana LG, Valpione S, Falci C, et al. The activity and safety of electrochemotherapy in persistent chest wall recurrence from breast cancer after mastectomy:a phase-Ⅱstudy[J]. Breast CancerRes Treat, 2012, 134(3):1169-1178.
3. Sinicropi D, Qu KB, Collin F, et al. Whole transcriptome RNA-Seqanalysis of breast cancer recurrence risk using formalin-fixed para-ffin-embedded tumor tissue [J]. PLoS One, 2012, 7(7):e40092.
4. Chen MH, Yip GW, Tse GM, et al. Expression of basal keratins and vimentin in breast cancers of young women correlates with adverse pathologic parameters[J]. Mod Pathol, 2008, 21(10):1183-1191.
5. Sheri A, Dowsett M. Developments in Ki67 and other biomarkers for treatment decision making in breast cancer[J]. Ann Oncol, 2012, 23 Suppl 10:x219-x227.
6. Wojnar A, Pula B, Piotrowska A, et al. Correlation of intensityof MT-Ⅰ/Ⅱ expression with Ki-67 and MCM-2 proteins in invasiveductal breast carcinoma[J]. Anticancer Res, 2011, 31(9):3027-3033.
7. Rakha EA, El-Sayed ME, Green AR, et al. Breast carcinoma with basal differentiation:a proposal for pathology definition based on basal cytokeratin expression[J]. Histopathology, 2007, 50(4):434-438.
8. Sutton LM, Han JS, Molberg KH, et al. Intratumoral expressionlevel of epidermal growth factor receptor and cytokeratin 5/6 issignificantly associated with nodal and distant metastases in patientswith basal-like triple-negative breast carcinoma[J]. Am J Clin Pathol, 2010, 134(5):782-787.
9. Choccalingam C, Rao L, Rao S. Clinicopathological characteristics of triple negative and non triple negative high grade breast carcinomas with and without basal marker (CK5/6 and EGFR)expression at a Rural Tertiary Hospital in India[J]. Breast Cancer(Auckl), 2012, 6:21-29.
10. Rakha EA, Ellis IO, Reis-Filho JS. Immunohistochemical heter-ogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2/neu (basal-like breast carcinomas)[J]. Mod Pathol, 2008, 21(8):1060-1061.
11. Turner NC, Reis-Filho JS, Russell AM, et al. BRCA1 dysfunctionin sporadic basal-like breast cancer[J]. Oncogene, 2007, 26(14):2126-2132.
12. Reis-Filho JS, Tutt AN. Triple negative tumours:a critical review[J]. Histopathology, 2008, 52(1):108-118.
13. Kobayashi T, Iwaya K, Moriya T, et al. A simple immunohistochemical panel comprising 2 conventional markers, Ki67 and p53, is a powerful tool for predicting patient outcome in luminal-type breast cancer[J]. BMC Clin Pathol, 2013, 13:5.
14. Klintman M, Bendahl PO, Grabau D, et al. The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer[J]. Mod Pathol, 2010, 23(2):251-259.
15. Bonta I, Bonta D, Loch MM, et al. Relationship of Ki67 to tumorsize and lymph node metastasis in breast cancer[J]. ASCO AnnualMeeting Proceedings (Post-Meeting Edition), 2012, 30(15):e21076.
16. Imamura H, Haga S, Shimizu T, et al. Prognostic significance of MIB1-determined proliferative activities in intraductal compon-ents and invasive foci associated with invasive ductal breast carcinoma[J]. Br J Cancer, 1999, 79(1):172-178.
17. Colozza M, Azambuja E, Cardoso F, et al. Proliferative markers as prognostic and predictive tools in early breast cancer:where are we now?[J]. Ann Oncol, 2005, 16(11):1723-1739.
18. Delpech Y, Wu Y, Hess KR, et al. Ki67 expression in the primarytumor predicts for clinical benefit and time to progression on first-lineendocrine therapy in estrogen receptor-positive metastatic breast cancer[J]. Breast Cancer Res Treat, 2012, 135(2):619-627.
19. Yoshioka T, Hosoda M, Yamamoto M, et al. Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast cancer[J]. Breast Cancer, 2013 May 5. [Epub ahead of print].
20. 余海云, 李文萍, 郜紅藝. 新輔助化療療效與乳腺癌Ki67、P53表達的關(guān)系[J/CD]. 中華乳腺外科雜志:電子版, 2011, 5(3):297-305.
21. Fasching PA, Heusinger K, Haeberle L, et al. Ki67, chemotherapyresponse, and prognosis in breast cancer patients receiving neoadjuvant treatment[J]. BMC Cancer, 2011, 11:486.
22. 吳俊東, 黃文河, 陳明, 等. 三陰性乳腺癌與HER-2過表達乳腺癌患者的臨床病理特征及預(yù)后比較[J]. 中華內(nèi)分泌外科雜志, 2011, 5(3):161-164.
23. 冷冬妮, 王海, 劉英娜, 等. 浸潤性乳腺癌中CK5/6、EGFR以及激素受體表達的相關(guān)性分析[J]. 現(xiàn)代腫瘤醫(yī)學, 2010, 18(6):1110-1113.
24. 管小青, 吳驥, 顧書成, 等. survivin與p53、Ki67在復(fù)發(fā)轉(zhuǎn)移性乳腺癌組織中表達及相關(guān)性研究[J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(3):290-294.
25. Goldhirsch A, Ingle JN, Gelber RD, et al. Thresholds for therapies:highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009[J]. Ann Oncol, 2009, 20(8):1319-1329.
26. Umemura S, Shirane M, Tkekoshi S. High expression of thymidine phosphorylase in basal-like breast cancers:Stromal expression in EGFR- and/or CK5/6-positive breast cancers[J]. Oncol Lett. 2010, 1(2):261-266.
27. 陳玉娟, 王曉東, 汪靜. 三陰乳腺癌的特征及治療現(xiàn)狀[J]. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(9):1024-1027.
  1. 1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012[J]. CA Cancer J Clin, 2012, 62(1):10-29.
  2. 2. Campana LG, Valpione S, Falci C, et al. The activity and safety of electrochemotherapy in persistent chest wall recurrence from breast cancer after mastectomy:a phase-Ⅱstudy[J]. Breast CancerRes Treat, 2012, 134(3):1169-1178.
  3. 3. Sinicropi D, Qu KB, Collin F, et al. Whole transcriptome RNA-Seqanalysis of breast cancer recurrence risk using formalin-fixed para-ffin-embedded tumor tissue [J]. PLoS One, 2012, 7(7):e40092.
  4. 4. Chen MH, Yip GW, Tse GM, et al. Expression of basal keratins and vimentin in breast cancers of young women correlates with adverse pathologic parameters[J]. Mod Pathol, 2008, 21(10):1183-1191.
  5. 5. Sheri A, Dowsett M. Developments in Ki67 and other biomarkers for treatment decision making in breast cancer[J]. Ann Oncol, 2012, 23 Suppl 10:x219-x227.
  6. 6. Wojnar A, Pula B, Piotrowska A, et al. Correlation of intensityof MT-Ⅰ/Ⅱ expression with Ki-67 and MCM-2 proteins in invasiveductal breast carcinoma[J]. Anticancer Res, 2011, 31(9):3027-3033.
  7. 7. Rakha EA, El-Sayed ME, Green AR, et al. Breast carcinoma with basal differentiation:a proposal for pathology definition based on basal cytokeratin expression[J]. Histopathology, 2007, 50(4):434-438.
  8. 8. Sutton LM, Han JS, Molberg KH, et al. Intratumoral expressionlevel of epidermal growth factor receptor and cytokeratin 5/6 issignificantly associated with nodal and distant metastases in patientswith basal-like triple-negative breast carcinoma[J]. Am J Clin Pathol, 2010, 134(5):782-787.
  9. 9. Choccalingam C, Rao L, Rao S. Clinicopathological characteristics of triple negative and non triple negative high grade breast carcinomas with and without basal marker (CK5/6 and EGFR)expression at a Rural Tertiary Hospital in India[J]. Breast Cancer(Auckl), 2012, 6:21-29.
  10. 10. Rakha EA, Ellis IO, Reis-Filho JS. Immunohistochemical heter-ogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2/neu (basal-like breast carcinomas)[J]. Mod Pathol, 2008, 21(8):1060-1061.
  11. 11. Turner NC, Reis-Filho JS, Russell AM, et al. BRCA1 dysfunctionin sporadic basal-like breast cancer[J]. Oncogene, 2007, 26(14):2126-2132.
  12. 12. Reis-Filho JS, Tutt AN. Triple negative tumours:a critical review[J]. Histopathology, 2008, 52(1):108-118.
  13. 13. Kobayashi T, Iwaya K, Moriya T, et al. A simple immunohistochemical panel comprising 2 conventional markers, Ki67 and p53, is a powerful tool for predicting patient outcome in luminal-type breast cancer[J]. BMC Clin Pathol, 2013, 13:5.
  14. 14. Klintman M, Bendahl PO, Grabau D, et al. The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer[J]. Mod Pathol, 2010, 23(2):251-259.
  15. 15. Bonta I, Bonta D, Loch MM, et al. Relationship of Ki67 to tumorsize and lymph node metastasis in breast cancer[J]. ASCO AnnualMeeting Proceedings (Post-Meeting Edition), 2012, 30(15):e21076.
  16. 16. Imamura H, Haga S, Shimizu T, et al. Prognostic significance of MIB1-determined proliferative activities in intraductal compon-ents and invasive foci associated with invasive ductal breast carcinoma[J]. Br J Cancer, 1999, 79(1):172-178.
  17. 17. Colozza M, Azambuja E, Cardoso F, et al. Proliferative markers as prognostic and predictive tools in early breast cancer:where are we now?[J]. Ann Oncol, 2005, 16(11):1723-1739.
  18. 18. Delpech Y, Wu Y, Hess KR, et al. Ki67 expression in the primarytumor predicts for clinical benefit and time to progression on first-lineendocrine therapy in estrogen receptor-positive metastatic breast cancer[J]. Breast Cancer Res Treat, 2012, 135(2):619-627.
  19. 19. Yoshioka T, Hosoda M, Yamamoto M, et al. Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast cancer[J]. Breast Cancer, 2013 May 5. [Epub ahead of print].
  20. 20. 余海云, 李文萍, 郜紅藝. 新輔助化療療效與乳腺癌Ki67、P53表達的關(guān)系[J/CD]. 中華乳腺外科雜志:電子版, 2011, 5(3):297-305.
  21. 21. Fasching PA, Heusinger K, Haeberle L, et al. Ki67, chemotherapyresponse, and prognosis in breast cancer patients receiving neoadjuvant treatment[J]. BMC Cancer, 2011, 11:486.
  22. 22. 吳俊東, 黃文河, 陳明, 等. 三陰性乳腺癌與HER-2過表達乳腺癌患者的臨床病理特征及預(yù)后比較[J]. 中華內(nèi)分泌外科雜志, 2011, 5(3):161-164.
  23. 23. 冷冬妮, 王海, 劉英娜, 等. 浸潤性乳腺癌中CK5/6、EGFR以及激素受體表達的相關(guān)性分析[J]. 現(xiàn)代腫瘤醫(yī)學, 2010, 18(6):1110-1113.
  24. 24. 管小青, 吳驥, 顧書成, 等. survivin與p53、Ki67在復(fù)發(fā)轉(zhuǎn)移性乳腺癌組織中表達及相關(guān)性研究[J]. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(3):290-294.
  25. 25. Goldhirsch A, Ingle JN, Gelber RD, et al. Thresholds for therapies:highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009[J]. Ann Oncol, 2009, 20(8):1319-1329.
  26. 26. Umemura S, Shirane M, Tkekoshi S. High expression of thymidine phosphorylase in basal-like breast cancers:Stromal expression in EGFR- and/or CK5/6-positive breast cancers[J]. Oncol Lett. 2010, 1(2):261-266.
  27. 27. 陳玉娟, 王曉東, 汪靜. 三陰乳腺癌的特征及治療現(xiàn)狀[J]. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(9):1024-1027.