Role of Lamin A and emerin in maintaining nuclear morphology in different subtypes of ovarian epithelial cancer

Shiori Watabe; Sayaka Kobayashi; Mizuho Hatori; Yoshimi Nishijima; Naoki Inoue; Hayato Ikota; Akira Iwase; Hideaki Yokoo; Masanao Saio

doi:10.3892/ol.2021.13127

Role of Lamin A and emerin in maintaining nuclear morphology in different subtypes of ovarian epithelial cancer

Oncol Lett. 2022 Jan;23(1):9. doi: 10.3892/ol.2021.13127. Epub 2021 Nov 9.

Authors

Shiori Watabe^{1

2}, Sayaka Kobayashi¹, Mizuho Hatori¹, Yoshimi Nishijima¹, Naoki Inoue³, Hayato Ikota⁴, Akira Iwase³, Hideaki Yokoo⁵, Masanao Saio¹

Affiliations

¹ Laboratory of Histopathology and Cytopathology, Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Gunma 371-8514, Japan.
² Department of Pathology, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-8605, Japan.
³ Department of Obstetrics and Gynecology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
⁴ Clinical Department of Pathology, Gunma University Hospital, Maebashi, Gunma 371-8511, Japan.
⁵ Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.

Abstract

The nuclear lamina protein, Lamin A and inner nuclear membrane protein, emerin participate in maintaining nuclear morphology. However, their correlations with the nuclear shape in the four representative ovarian epithelial cancer subtypes, high-grade serous carcinoma (HGSCa), clear cell carcinoma (CCCa), endometrioid carcinoma (EMCa) and mucinous carcinoma (MUCa), remains unclear. The present study aimed to investigate the association between nuclear morphology and nuclear membrane protein expression in four histological subtypes of ovarian epithelial cancer. A total of 140 surgically resected ovarian cancer specimens were subjected to Feulgen staining to evaluate nuclear morphology, and immunohistochemistry analysis to assess Lamin A and emerin expression. The histological images were analyzed via computer-assisted image analysis (CAIA). The results demonstrated that the mean nuclear area of EMCa was significantly smaller compared with CCCa (P=0.0009). The standard deviation of the mean nuclear area was used to assess nuclear size variation, and the results indicated that EMCa lesions were significantly smaller than CCCa lesions (P=0.0006). Regarding the correlation between the Lamin A-positive rate and nuclear morphological factors, positive correlations were observed with nuclear area in CCCa and EMCa (R=0.2855 and R=0.2858, respectively) and nuclear perimeter in CCCa, EMCa and MUCa (R=0.2409, R=0.4054 and R=0.2370, respectively); however, a negative correlation with nuclear shape factor was observed in HGSCa and EMCa (R=-0.2079 and R=-0.3707, respectively). With regards to the correlation between emerin positivity and nuclear morphological factors, positive correlations were observed with nuclear shape factor in HGSCa (R=0.2673) and nuclear area in CCCa (R=0.3310). It is well-known that HGSCa and CCCa have conspicuous nuclear size variation, and EMCa has small nuclei without strong atypia. These findings were verified in the present study via CAIA. Taken together, the results of the present study suggest that Lamin A strongly contributes to the maintenance of nuclear morphology in ovarian epithelial cancer compared with emerin, although their contributions differ based on tumor subtype.

Keywords: Lamin A; computer-assisted image analysis; emerin; nuclear morphology; ovarian cancer.

Grants and funding

The present study was supported by a research fund from Gunma University and by JSPS KAKENHI (grant no. JP21K09533).