19q13.41

NES1,PRSSL1

Various cancers with upragulated KLK10.

Epithelial ovarian carcinoma, uterine serous papillary carcinoma, head and neck squamous cell carcinoma, lung squamous cell carcinoma, and gastrointestinal tract cancer.

In these malignancies, KLK10 has been reported to be upregulated. Among them, epithelial ovarian carcinoma is by far studied the most. KLK10 is overexpressed in ovarian tumor tissue than in normal epithelium and stromal tissues both at the mRNA and protein levels. Due to increased leakage of KLK10 into the circulation, serum concentrations of KLK10 in ovarian cancer patients are elevated. High levels of KLK10 in tumor tissue or in serum are associated with more advanced disease stages and poor survival. In particular, preoperative serum KLK10 levels can serve as a complimentary biomarker for CA125, a well-established tumor marker routinely used in ovarian cancer. It has been demonstrated that nearly all CA125-negative tumors show KLK10 immunostaining positivity and that about 35% of CA125-negative patients have increased serum levels of KLK10. In combination with CA125, KLK10 can improve the diagnostic sensitivity by about 20% compared to that of CA125 alone.

No cytogenetic abnormalities are identified so far.

Not identified so far.

Various cancers with down regulated KLK10.

Breast cancer, testicular cancer, leukemia, and prostate cancer.

In contrast to ovarian cancer, KLK10 is down regulated in these malignancies, with breast cancer as a prototype. Several lines of evidence have demonstrated that KLK10 is progressively down regulated during breast cancer development. In a clinical study, it is observed that essentially all normal breast specimens had KLK10 expression, whereas about 46% of ductal carcinoma in situ (DCIS) and the majority of infiltrating ductal carcinoma (IDC) had no detectable KLK10 expression. More importantly, the KLK10 negative-DCIS was found to subsequently develop to IDC. In in vitro studies, it has been shown that KLK10 is expressed in normal breast epithelial cells but dramatically reduced in breast cancer cell lines. Moreover, reintroduction of KLK10 expression into these cancer cells can suppress their tumorigenecity in nude mice. KLK10 was thus considered to function as a tumor suppressor in breast cancer. The mechanisms governing the down regulation of KLK10 in breast cancer is not clear. One explanation is CpG island hypermethylation of exon 3, as demonstrated in a number of cancer cell lines. Noteworthy, expression of KLK10 is modulated by some steroid hormones and retinoid acid. They may, under certain conditions, also contribute to the aberrant expression of KLK10 in tumor tissues. However, the paradoxical expression of KLK10 in different types of tumors remains obscure.