Clinical Significance of Combined Detection of Expressions of CK5/6 and Ki-67 in Breast Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Jinan , MA Zhenhai , XU Jingchao ,  ZHAO Yongfu

Department of General Surgery， The Second Affiliated Hospital of Dalian Medical University， Dalian 116023， Liaoning Province， China;

Corresponding author：

ZHAO Yongfu, Email: dl.zyf67@163.com

Keywords：

Breast cancer; CK5/6; Ki-67; Immunohistochemistry

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Objective 　To detect the expressions of CK5/6 and Ki-67 in breast cancer， and explore the clinical significance.
Methods 　The expressions of CK5/6 and Ki-67 were detected by immunohistochemistry in 162 cases of breast cancer . The correlation between CK5/6 expression and Ki-67 expression and the relationship of the expressions of two factors to the clinicopathologic factors were analyzed.
Results　 There were 12 cases of the triple negative breast cancer 〔negative estrogen receptor （ER）， negative progesterone receptor （PR）， and negative Her-2〕 in 162 patients with　breast cancer. The positive rates of CK5/6 and Ki-67 in the breast cancer tissues were 30.9% （50/162） and 65.4% （106/162），respectively. The positive rates of CK5/6 and Ki-67 in the patients with triple negative breast cancer were significantly higher than those of non-triple negative breast cancer 〔CK5/6：75.0% （9/12） versus 27.3% （41/150）， χ2=11.837， P=0.001；Ki-67：100% （12/12） versus 62.7% （94/150）， χ2=6.847， P=0.009〕. The expressions of CK5/6 and Ki-67 in the breast cancer tissues were not associated with age （P＞0.05）， but they were associated with histology grade （P＜0.05）. The expression of CK5/6 wasn’t associated with tumor size and lymph node status （P＞0.05）， but the expression of　Ki-67 was associated with them （P＜0.05）. The expression of CK5/6 in the breast cancer tissue had a positive correlation　with the expression of Ki-67 in the breast cancer tissue （rs=0.271， P=0.000）. There were 64 cases when the expression of Ki-67 was （＋＋） and （＋＋＋）， the positive rate of CK5/6 was 43.8% （28/64） and it was significantly higher than that when the expression of Ki-67 was （-） and （＋）〔22.4% （22/98）， χ2=8.233， P=0.004〕. The positive expressions of CK5/6 and Ki-67 in the breast cancer tissues were negatively correlated with the expressions of ER and PR （CK5/6 and　ER：rs=-0.446， P=0.000；CK5/6 and PR：rs=-0.370， P=0.000；Ki-67 and ER：rs=-0.518， P=0.000；Ki-67 and PR：rs=-0.515， P=0.000）. The positive expressions of CK5/6 and Ki-67 in the breast cancer tissue were not correlated with the Her-2 expression （CK5/6 and Her-2：rs=0.105， P=0.183；Ki-67 and Her-2：rs=0.068， P=0.393）.
Conclusion 　The expressions of CK5/6 and Ki67 not only can evaluate the basic rules of breast cancer from origin and development， but also they are beneficial to choose the chemotherapy of different patients.

Citation： LI Jinan,MA Zhenhai,XU Jingchao,ZHAO Yongfu. Clinical Significance of Combined Detection of Expressions of CK5/6 and Ki-67 in Breast Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(11): 1245-1249. doi: Copy

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，郜红艺. 新辅助化疗疗效与乳腺癌Ki67、P53表达的关系[J/CD]. 中华乳腺外科杂志：电子版， 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.	吴俊东，黄文河，陈明，等. 三阴性乳腺癌与HER-2过表达乳腺癌患者的临床病理特征及预后比较[J]. 中华内分泌外科杂志， 2011， 5(3)：161-164.
23.	冷冬妮，王海，刘英娜，等. 浸润性乳腺癌中CK5/6、EGFR以及激素受体表达的相关性分析[J]. 现代肿瘤医学， 2010， 18(6)：1110-1113.
24.	管小青，吴骥，顾书成，等. survivin与p53、Ki67在复发转移性乳腺癌组织中表达及相关性研究[J]. 中国普外基础与临床杂志， 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.	陈玉娟，王晓东，汪静. 三阴乳腺癌的特征及治疗现状[J]. 中国普外基础与临床杂志， 2012， 19(9)：1024-1027.

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，郜红艺. 新辅助化疗疗效与乳腺癌Ki67、P53表达的关系[J/CD]. 中华乳腺外科杂志：电子版， 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. 吴俊东，黄文河，陈明，等. 三阴性乳腺癌与HER-2过表达乳腺癌患者的临床病理特征及预后比较[J]. 中华内分泌外科杂志， 2011， 5(3)：161-164.
23. 冷冬妮，王海，刘英娜，等. 浸润性乳腺癌中CK5/6、EGFR以及激素受体表达的相关性分析[J]. 现代肿瘤医学， 2010， 18(6)：1110-1113.
24. 管小青，吴骥，顾书成，等. survivin与p53、Ki67在复发转移性乳腺癌组织中表达及相关性研究[J]. 中国普外基础与临床杂志， 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. 陈玉娟，王晓东，汪静. 三阴乳腺癌的特征及治疗现状[J]. 中国普外基础与临床杂志， 2012， 19(9)：1024-1027.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Clinical Significance of Combined Detection of Expressions of CK5/6 and Ki-67 in Breast Cancer

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