Aberrant Nuclear Localization of aPKCλ/ι is Associated With Poorer Prognosis in Uterine Cervical Cancer

We previously reported that aberrant expression of atypical protein kinase C lambda/iota (aPKC lambda/iota) in low-grade squamous intraepithelial uterine cervix lesions was associated with an increased risk of progression to higher grade. This study aimed to investigate aPKC lambda/iota expression patterns in cervical squamous cell carcinoma (SCC) and its association with disease progression. We immunohistochemically assessed aPKC lambda/iota expression in 168 SCC samples and 13 normal uterine cervix samples. In 69.0% of SCC cases, aPKC lambda/iota was expressed more abundantly than in normal epithelium, but there was no significant association between aPKC lambda/iota intensity and disease progression (P=0.087, Cochran-Mantel-Haenszel test). aPKC lambda/iota in normal cervical epithelium was confined to the cytoplasm or intercellular junctions. In contrast, aPKC lambda/iota was predominantly localized within the nucleus in 36.9% of SCC samples (P<0.001, chi(2) test), and the prevalence was significantly increased relative to advanced tumor stage (P<0.001, Cochran-Mantel-Haenszel test). Moreover, patients with SCC with aPKC lambda/iota nuclear localization had worse prognoses than those with cytoplasmic localization (P<0.001, log-rank test). aPKC lambda/iota localization differed between the intraepithelial lesion and adjacent invasive cancer in 40% of cases, while the expression pattern was similar between primary and matched metastatic tumors. In conclusion, aPKC lambda/iota nuclear localization in cervical cancer is associated with tumor progression and worse prognosis. This is the first report to show aberrant nuclear aPKC lambda/iota localization in a subgroup of cervical cancer patients and its association with worse prognosis.