The prognostic potential of keratin 18 in breast cancer associated with tumor dedifferentiation, and the loss of estrogen and progesterone receptors.
The differential expression profiling with breast normal and tumor tissues, and a breast cancer cell line led to identification of cytokeratin 18 (KT18) gene over-expressed in breast cancer. The expression pattern of KT18 in breast cancer was compared to those of conventional tumor markers such as proliferating cell nuclear antigen (PCNA) and minichromosome maintenance protein 3 (MCM3). Their expression patterns in breast cancer were almost identical, suggesting that KT18 might be useful for detection of proliferating fractions in the breast cancer. The immunohistochemical analyses on the tissue microarray consisting of invasive ductal carcinomas revealed that the up-regulation of KT18 is observed in a majority of breast carcinomas whereas its down-regulation also occurs at a less frequency. Of particular interest, KT18 down-regulation was associated with histologically poorly differentiated carcinomas than well differentiated carcinomas. In addition, it was also significantly associated with the loss of estrogen receptor (ER) and progesterone receptor (PR), the prognostic markers of the breast cancer (P < 0.05), while not with HER2, tumor size, and lymph node metastasis. This result suggests that KT18 correlated with ER and PR may be utilized for the prognosis of breast cancer. Furthermore, the forced down-regulation of KT18 enhanced the growth of tumor xenografts in vivo and invasiveness in vitro. Therefore, our findings suggest that loss of KT18 expression might be a good indicator of the poor prognosis of the breast cancer and it may play an active role in the breast tumorigenesis.
Molecular Genetic Laboratory and Departments of Clinical Pathology and Gynecology College of Medicine, The Catholic University of Korea, Seoul, Korea.
Seon-Ah
SA
Ha
Youn Soo
YS
Lee
Hyun Kee
HK
Kim
Jinah
J
Yoo
Sanghee
S
Kim
Gi-Hwan
GH
Gong
Youn Kyung
YK
Lee
Jin Woo
JW
Kim
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054337:Cell Dedifferentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053538:Keratin-18 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D053538:Keratin-18; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone