Image analysis of the nuclear characteristics of emerin protein and the correlation with nuclear grooves and intranuclear cytoplasmic inclusions in lung adenocarcinoma

Kobayashi,Sayaka; Saio,Masanao; Fukuda,Toshio; Kimura,Kiminori; Hirato,Junko; Oyama,Tetsunari

doi:10.3892/or.2018.6848

Image analysis of the nuclear characteristics of emerin protein and the correlation with nuclear grooves and intranuclear cytoplasmic inclusions in lung adenocarcinoma

Authors:
- Sayaka Kobayashi
- Masanao Saio
- Toshio Fukuda
- Kiminori Kimura
- Junko Hirato
- Tetsunari Oyama
View Affiliations

Affiliations: Laboratory of Histopathology and Cytopathology, Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma 371-8514, Japan, Department of Hepatology, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo 113-8677, Japan, Department of Pathology, Gunma University Hospital, Gunma 371-8511, Japan
Published online on: November 2, 2018 https://doi.org/10.3892/or.2018.6848
Pages: 133-142
Copyright: © Kobayashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Nuclear size and shape are important components in the diagnosis of pathological specimens. However, a qualitative evaluation is typically applied rather than a quantitative evaluation technique. In the present study, we sought to evaluate the nuclear morphological characteristics of lung adenocarcinoma using whole-slide imaging (WSI) and computer-assisted image analysis (IA). We evaluated the nuclear characteristics of 106 cases of surgically resected lung adenocarcinoma according to Feulgen staining and immunohistochemistry (IHC) for the inner nuclear membrane protein emerin. According to the Feulgen reaction, although the nuclear area (size) of the carcinoma cells was correlated with the nuclear perimeter (NP) (R=0.8973), the nuclear staining intensity of carcinoma cells was not correlated with the nuclear area. Using emerin IHC, we used IA software that was able to detect both the NP and the emerin-stained nuclear membrane length (ENML) in the nucleus, and found that the more nuclei exhibited a longer ENML relative to the NP, the more nuclear grooves and intranuclear cytoplasmic inclusions were present. In addition, the nuclear area was correlated with the percentage of nuclei that had a longer ENML compared to the NP against the total nuclei (R=0.7759). Furthermore, the emerin low expression group showed an enlarged nuclear area (P=0.0264), elongated NP (P=0.0091), and lower shape factor (P=0.0486) compared with the normal emerin expression group. Our data indicated the usefulness of WSI and IA for pathological specimen analysis. In addition, this study is the first to report that the low expression of emerin in cancer cell results in an oval shape of nuclei and nuclear enlargement in clinical samples.

View Figures

View References

1	Nakazato Y, Maeshima AM, Ishikawa Y, Yatabe Y, Fukuoka J, Yokose T, Tomita Y, Minami Y, Asamura H, Tachibana K, et al: Interobserver agreement in the nuclear grading of primary pulmonary adenocarcinoma. J Thorac Oncol. 8:736–743. 2013. View Article : Google Scholar : PubMed/NCBI
2	Stern E, Rosenthal DL, McLatchie C, White BS and Castleman KR: An expanded cervical cell classification system validated by automated measurements. Anal Quant Cytol. 4:110–114. 1982.PubMed/NCBI
3	Rosenthal DL, McLatchie C, Stern E, White BS and Castleman KR: Endocervical columnar cell atypia coincident with cervical neoplasia characterized by digital image analysis. Acta Cytol. 26:115–120. 1982.PubMed/NCBI
4	Nakazato Y, Minami Y, Kobayashi H, Satomi K, Anami Y, Tsuta K, Tanaka R, Okada M, Goya T and Noguchi M: Nuclear grading of primary pulmonary adenocarcinomas: Correlation between nuclear size and prognosis. Cancer. 116:2011–2019. 2010. View Article : Google Scholar : PubMed/NCBI
5	Yamada M, Saito A, Yamamoto Y, Cosatto E, Kurata A, Nagao T, Tateishi A and Kuroda M: Quantitative nucleic features are effective for discrimination of intraductal proliferative lesions of the breast. J Pathol Inform. 7:12016. View Article : Google Scholar : PubMed/NCBI
6	Kosuge N, Saio M, Matsumoto H, Aoyama H, Matsuzaki A and Yoshimi N: Nuclear features of infiltrating urothelial carcinoma are distinguished from low-grade noninvasive papillary urothelial carcinoma by image analysis. Oncol Lett. 14:2715–2722. 2017. View Article : Google Scholar : PubMed/NCBI
7	Webster M, Witkin KL and Cohen-Fix O: Sizing up the nucleus: Nuclear shape, size and nuclear-envelope assembly. J Cell Sci. 122:1477–1486. 2009. View Article : Google Scholar : PubMed/NCBI
8	Asioli S and Bussolati G: Emerin immunohistochemistry reveals diagnostic features of nuclear membrane arrangement in thyroid lesions. Histopathology. 54:571–579. 2009. View Article : Google Scholar : PubMed/NCBI
9	Bussolati G, Marchiò C, Gaetano L, Lupo R and Sapino A: Pleomorphism of the nuclear envelope in breast cancer: A new approach to an old problem. J Cell Mol Med. 12:209–218. 2008. View Article : Google Scholar : PubMed/NCBI
10	O'Sullivan B, Mason M, Asmura H, Lee A, Van Eychen E, Denny L, MB A and Gupta S: Lung. In: TNM Classification of Malignant Tumours, Eighth Edition. Brierley JD, Gospodarowicz MK and Wittekind C: Wiley Blackwell; West Sussex; pp. 106–112. 2017
11	Travis W, Ladanyi M, Scagliotti G, Noguchi M, Meyerson M, Thunnissen E, Yatabe Y, Mino-Kenudson M, To K, Brambilla E, et al: Adenocarcinoma: WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. Travis W, Brambilla E, Burke A, Marx A and Nicholson A: International Agency for Research on Cancer Lyon. 26–37. 2015.
12	Kreicbergs A and Zetterberg A: Cytophotometric DNA measurements of chondrosarcoma: Methodologic aspects of measurements in tissue sections from old paraffin-embedded specimens. Anal Quant Cytol. 2:84–92. 1980.PubMed/NCBI
13	Akobeng AK: Understanding diagnostic tests 3: Receiver operating characteristic curves. Acta Paediatr. 96:644–647. 2007. View Article : Google Scholar : PubMed/NCBI
14	Fischer A: The diagnostic pathology of the nuclear envelope in human cancers. In: Cancer Biology and the Nuclear Envelope. Schirmer EC and de las Heras JI: Springer; London: pp. 49–75. 2014
15	Kumar M, Chatterjee K, Purkait SK and Samaddar D: Computer-assisted morphometric image analysis of cells of normal oral epithelium and oral squamous cell carcinoma. J Oral Maxillofac Pathol. 21:24–29. 2017. View Article : Google Scholar : PubMed/NCBI
16	Kashyap A, Jain M, Shukla S and Andley M: Role of nuclear morphometry in breast cancer and its correlation with cytomorphological grading of breast cancer: A study of 64 cases. J Cytol. 35:41–45. 2018. View Article : Google Scholar : PubMed/NCBI
17	Biesterfeld S, Beckers S, Del Carmen Villa Cadenas M and Schramm M: Feulgen staining remains the gold standard for precise DNA image cytometry. Anticancer Res. 31:53–58. 2011.PubMed/NCBI
18	Lee JH, Han EM, Lin ZH, Wu ZS, Lee ES and Kim YS: Clinicopathologic significance of nuclear grooves and inclusions in renal cell carcinoma: Image database construction and quantitative scoring. Arch Pathol Lab Med. 132:940–946. 2008.PubMed/NCBI
19	Naka M, Ohishi Y, Kaku T, Watanabe S, Tamiya S, Ookubo F, Kato K, Oda Y and Sugishima S: Identification of intranuclear inclusions is useful for the cytological diagnosis of ovarian clear cell carcinoma. Diagn Cytopathol. 43:879–884. 2015. View Article : Google Scholar : PubMed/NCBI
20	Das DK: Intranuclear cytoplasmic inclusions in fine-needle aspiration smears of papillary thyroid carcinoma: A study of its morphological forms, association with nuclear grooves, and mode of formation. Diagn Cytopathol. 32:264–268. 2005. View Article : Google Scholar : PubMed/NCBI
21	Choi IH, Kim DW, Ha SY, Choi YL, Lee HJ and Han J: Analysis of histologic features suspecting anaplastic lymphoma kinase (ALK)-expressing pulmonary adenocarcinoma. J Pathol Transl Med. 49:310–317. 2015. View Article : Google Scholar : PubMed/NCBI
22	Koch AJ and Holaska JM: Emerin in health and disease. Semin Cell Dev Biol. 29:95–106. 2014. View Article : Google Scholar : PubMed/NCBI
23	Koch AJ and Holaska JM: Loss of emerin alters myogenic signaling and miRNA expression in mouse myogenic progenitors. PLoS One. 7:e372622012. View Article : Google Scholar : PubMed/NCBI
24	Holaska JM and Wilson KL: Multiple roles for emerin: Implications for Emery-Dreifuss muscular dystrophy. Anat Rec A Discov Mol Cell Evol Biol. 288:676–680. 2006. View Article : Google Scholar : PubMed/NCBI
25	Jieying W, Kondo T, Yamane T, Nakazawa T, Oishi N, Kawasaki T, Mochizuki K, Dongfeng N and Katoh R: Heterogeneous immunoreactivity of emerin, a nuclear envelope LEM-domain protein, in normal thyroid follicles. Acta Histochem Cytochem. 47:289–294. 2014. View Article : Google Scholar : PubMed/NCBI
26	Smith ER, Meng Y, Moore R, Tse JD, Xu AG and Xu XX: Nuclear envelope structural proteins facilitate nuclear shape changes accompanying embryonic differentiation and fidelity of gene expression. BMC Cell Biol. 18:82017. View Article : Google Scholar : PubMed/NCBI
27	Lammerding J, Hsiao J, Schulze PC, Kozlov S, Stewart CL and Lee RT: Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells. J Cell Biol. 170:781–791. 2005. View Article : Google Scholar : PubMed/NCBI