Aberrant nuclear localization of aPKCλ/ι is associated with poorer prognosis in uterine cervical cancer

Aya Tokinaga-Uchiyama, Taichi Mizushima, Kazunori Akimoto, Yoji Nagashima, Kazunori Sasaki, Masa Aki Nakaya, Kenichi Ohashi, Kazumi Kubota, Yasuyo Maruyama, Hisamori Kato, Fumiki Hirahara, Etsuko Miyagi, Shigeo Ohno, Mikiko Asai-Sato

Research output: Contribution to journalArticle

Abstract

We previously reported that aberrant expression of atypical protein kinase C λ/ι (aPKCλ/ι) in low-grade squamous intraepithelial uterine cervix lesions was associated with an increased risk of progression to higher grade. This study aimed to investigate aPKCλ/ι expression patterns in cervical squamous cell carcinoma (SCC) and its association with disease progression. We immunohistochemically assessed aPKCλ/ι expression in 168 SCC samples and 13 normal uterine cervix samples. In 69.0% of SCC cases, aPKCλ/ι was expressed more abundantly than in normal epithelium, but there was no significant association between aPKCλ/ι intensity and disease progression (P=0.087, Cochran-Mantel-Haenszel test). aPKCλ/ι in normal cervical epithelium was confined to the cytoplasm or intercellular junctions. In contrast, aPKCλ/ι was predominantly localized within the nucleus in 36.9% of SCC samples (P<0.001, χ2 test), and the prevalence was significantly increased relative to advanced tumor stage (P<0.001, Cochran-Mantel-Haenszel test). Moreover, patients with SCC with aPKCλ/ι nuclear localization had worse prognoses than those with cytoplasmic localization (P<0.001, log-rank test). aPKCλ/ι 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, aPKCλ/ι nuclear localization in cervical cancer is associated with tumor progression and worse prognosis. This is the first report to show aberrant nuclear aPKCλ/ι localization in a subgroup of cervical cancer patients and its association with worse prognosis.

Original languageEnglish
Pages (from-to)301-309
Number of pages9
JournalInternational Journal of Gynecological Pathology
Volume38
Issue number4
DOIs
Publication statusPublished - 1 Jul 2019

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Uterine Cervical Neoplasms
Squamous Cell Carcinoma
Cervix Uteri
Disease Progression
Neoplasms
PKC-3 protein
Epithelium
Intercellular Junctions
Nuclear Proteins
Cytoplasm

Keywords

  • Atypical protein kinase C
  • Cervical cancer
  • Cervical intraepithelial neoplasm
  • Prognostic factors

Cite this

Tokinaga-Uchiyama, Aya ; Mizushima, Taichi ; Akimoto, Kazunori ; Nagashima, Yoji ; Sasaki, Kazunori ; Nakaya, Masa Aki ; Ohashi, Kenichi ; Kubota, Kazumi ; Maruyama, Yasuyo ; Kato, Hisamori ; Hirahara, Fumiki ; Miyagi, Etsuko ; Ohno, Shigeo ; Asai-Sato, Mikiko. / Aberrant nuclear localization of aPKCλ/ι is associated with poorer prognosis in uterine cervical cancer. In: International Journal of Gynecological Pathology. 2019 ; Vol. 38, No. 4. pp. 301-309.
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title = "Aberrant nuclear localization of aPKCλ/ι is associated with poorer prognosis in uterine cervical cancer",
abstract = "We previously reported that aberrant expression of atypical protein kinase C λ/ι (aPKCλ/ι) in low-grade squamous intraepithelial uterine cervix lesions was associated with an increased risk of progression to higher grade. This study aimed to investigate aPKCλ/ι expression patterns in cervical squamous cell carcinoma (SCC) and its association with disease progression. We immunohistochemically assessed aPKCλ/ι expression in 168 SCC samples and 13 normal uterine cervix samples. In 69.0{\%} of SCC cases, aPKCλ/ι was expressed more abundantly than in normal epithelium, but there was no significant association between aPKCλ/ι intensity and disease progression (P=0.087, Cochran-Mantel-Haenszel test). aPKCλ/ι in normal cervical epithelium was confined to the cytoplasm or intercellular junctions. In contrast, aPKCλ/ι was predominantly localized within the nucleus in 36.9{\%} of SCC samples (P<0.001, χ2 test), and the prevalence was significantly increased relative to advanced tumor stage (P<0.001, Cochran-Mantel-Haenszel test). Moreover, patients with SCC with aPKCλ/ι nuclear localization had worse prognoses than those with cytoplasmic localization (P<0.001, log-rank test). aPKCλ/ι 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, aPKCλ/ι nuclear localization in cervical cancer is associated with tumor progression and worse prognosis. This is the first report to show aberrant nuclear aPKCλ/ι localization in a subgroup of cervical cancer patients and its association with worse prognosis.",
keywords = "Atypical protein kinase C, Cervical cancer, Cervical intraepithelial neoplasm, Prognostic factors",
author = "Aya Tokinaga-Uchiyama and Taichi Mizushima and Kazunori Akimoto and Yoji Nagashima and Kazunori Sasaki and Nakaya, {Masa Aki} and Kenichi Ohashi and Kazumi Kubota and Yasuyo Maruyama and Hisamori Kato and Fumiki Hirahara and Etsuko Miyagi and Shigeo Ohno and Mikiko Asai-Sato",
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Tokinaga-Uchiyama, A, Mizushima, T, Akimoto, K, Nagashima, Y, Sasaki, K, Nakaya, MA, Ohashi, K, Kubota, K, Maruyama, Y, Kato, H, Hirahara, F, Miyagi, E, Ohno, S & Asai-Sato, M 2019, 'Aberrant nuclear localization of aPKCλ/ι is associated with poorer prognosis in uterine cervical cancer', International Journal of Gynecological Pathology, vol. 38, no. 4, pp. 301-309. https://doi.org/10.1097/PGP.0000000000000539

Aberrant nuclear localization of aPKCλ/ι is associated with poorer prognosis in uterine cervical cancer. / Tokinaga-Uchiyama, Aya; Mizushima, Taichi; Akimoto, Kazunori; Nagashima, Yoji; Sasaki, Kazunori; Nakaya, Masa Aki; Ohashi, Kenichi; Kubota, Kazumi; Maruyama, Yasuyo; Kato, Hisamori; Hirahara, Fumiki; Miyagi, Etsuko; Ohno, Shigeo; Asai-Sato, Mikiko.

In: International Journal of Gynecological Pathology, Vol. 38, No. 4, 01.07.2019, p. 301-309.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aberrant nuclear localization of aPKCλ/ι is associated with poorer prognosis in uterine cervical cancer

AU - Tokinaga-Uchiyama, Aya

AU - Mizushima, Taichi

AU - Akimoto, Kazunori

AU - Nagashima, Yoji

AU - Sasaki, Kazunori

AU - Nakaya, Masa Aki

AU - Ohashi, Kenichi

AU - Kubota, Kazumi

AU - Maruyama, Yasuyo

AU - Kato, Hisamori

AU - Hirahara, Fumiki

AU - Miyagi, Etsuko

AU - Ohno, Shigeo

AU - Asai-Sato, Mikiko

PY - 2019/7/1

Y1 - 2019/7/1

N2 - We previously reported that aberrant expression of atypical protein kinase C λ/ι (aPKCλ/ι) in low-grade squamous intraepithelial uterine cervix lesions was associated with an increased risk of progression to higher grade. This study aimed to investigate aPKCλ/ι expression patterns in cervical squamous cell carcinoma (SCC) and its association with disease progression. We immunohistochemically assessed aPKCλ/ι expression in 168 SCC samples and 13 normal uterine cervix samples. In 69.0% of SCC cases, aPKCλ/ι was expressed more abundantly than in normal epithelium, but there was no significant association between aPKCλ/ι intensity and disease progression (P=0.087, Cochran-Mantel-Haenszel test). aPKCλ/ι in normal cervical epithelium was confined to the cytoplasm or intercellular junctions. In contrast, aPKCλ/ι was predominantly localized within the nucleus in 36.9% of SCC samples (P<0.001, χ2 test), and the prevalence was significantly increased relative to advanced tumor stage (P<0.001, Cochran-Mantel-Haenszel test). Moreover, patients with SCC with aPKCλ/ι nuclear localization had worse prognoses than those with cytoplasmic localization (P<0.001, log-rank test). aPKCλ/ι 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, aPKCλ/ι nuclear localization in cervical cancer is associated with tumor progression and worse prognosis. This is the first report to show aberrant nuclear aPKCλ/ι localization in a subgroup of cervical cancer patients and its association with worse prognosis.

AB - We previously reported that aberrant expression of atypical protein kinase C λ/ι (aPKCλ/ι) in low-grade squamous intraepithelial uterine cervix lesions was associated with an increased risk of progression to higher grade. This study aimed to investigate aPKCλ/ι expression patterns in cervical squamous cell carcinoma (SCC) and its association with disease progression. We immunohistochemically assessed aPKCλ/ι expression in 168 SCC samples and 13 normal uterine cervix samples. In 69.0% of SCC cases, aPKCλ/ι was expressed more abundantly than in normal epithelium, but there was no significant association between aPKCλ/ι intensity and disease progression (P=0.087, Cochran-Mantel-Haenszel test). aPKCλ/ι in normal cervical epithelium was confined to the cytoplasm or intercellular junctions. In contrast, aPKCλ/ι was predominantly localized within the nucleus in 36.9% of SCC samples (P<0.001, χ2 test), and the prevalence was significantly increased relative to advanced tumor stage (P<0.001, Cochran-Mantel-Haenszel test). Moreover, patients with SCC with aPKCλ/ι nuclear localization had worse prognoses than those with cytoplasmic localization (P<0.001, log-rank test). aPKCλ/ι 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, aPKCλ/ι nuclear localization in cervical cancer is associated with tumor progression and worse prognosis. This is the first report to show aberrant nuclear aPKCλ/ι localization in a subgroup of cervical cancer patients and its association with worse prognosis.

KW - Atypical protein kinase C

KW - Cervical cancer

KW - Cervical intraepithelial neoplasm

KW - Prognostic factors

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DO - 10.1097/PGP.0000000000000539

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JF - International Journal of Gynecological Pathology

SN - 0277-1691

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