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Article

Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma

  • Authors:
    • Rio Shibanuma
    • Sayaka Kobayashi
    • Momoka Konno
    • Rio Kaneko
    • Yoshimi Nishijima
    • Hayato Ikota
    • Masashi Nomura
    • Kazuhiro Suzuki
    • Hideaki Yokoo
    • Masanao Saio
  • View Affiliations / Copyright

    Affiliations: Laboratory of Histopathology and Cytopathology, Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Gunma 371‑8514, Japan, Clinical Department of Pathology, Gunma University Hospital, Maebashi, Gunma 371‑8511, Japan, Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan
  • Article Number: 86
    |
    Published online on: December 23, 2025
       https://doi.org/10.3892/ol.2025.15439
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Abstract

Clear cell renal cell carcinoma (ccRCC) nuclear grade is associated with patient prognosis. Currently, the World Health Organization (WHO)/International Society of Urologic Pathologists (ISUP) grading system is used to evaluate nuclear and cellular morphology. The present study aimed to investigate the relationship between nuclear envelope‑associated protein expression and nuclear grade. A total of 199 patients diagnosed with ccRCC were included in the study. Following immunohistochemical staining for Lamin A, Lamin B1, Lamin B2, Emerin, SUN1, SUN2, Nesprin‑1, Nesprin‑2 and Nesprin‑3, their expression levels were evaluated. Comparing the nuclear grade with the mean nuclear area and perimeter revealed a significant increase across each grade from G1 to G3. However, the difference between G3 and G4 was not significant, indicating that nuclear morphology in G4 may be influenced by another factor. Comparison of Lamin expression across nuclear grades showed that only Lamin A was significantly decreased in G4 cases. Furthermore, the positive rates of Lamin B1 and Lamin B2, as well as nuclear grade, did not differ significantly between the grades. Next, the association between changes in Emerin, SUN and Nesprin expression and nuclear grade was examined; notably, only SUN1 showed significant changes in G4, whereas no significant differences were observed between nuclear grade and the other proteins. Therefore, reduced Lamin A and SUN1 expression may cause morphological changes in the nucleus and cells, leading to a shift toward G4. The total volumes of the nucleus and nucleoli showed an isometric relationship. Thus, evaluating the nucleolus using nuclear grade classification in G1‑G3 ccRCC is essentially equivalent to evaluating the size of the nucleus. In conclusion, in the WHO/ISUP grading system, G1, G2 and G3 rely solely on nucleolar size as an indicator. However, in G4, both nuclear and cell morphology may be considered as indicators, since changes in nuclear envelope‑associated proteins were only detected in this grade.
View Figures

Figure 1

Comparison of nuclear size and
nuclear grade. (A) Mean nuclear area vs. Fuhrman grade. (B) Mean
nuclear area vs. the WHO/ISUP grading system. (C) Mean nuclear
perimeter vs. Fuhrman grade. (D) Mean nuclear perimeter vs. the
WHO/ISUP grading system. In the box-and-whisker plots, ‘X’
indicates the mean value; horizontal lines represent the median and
interquartile range, and the whiskers denote the minimum and
maximum values. P-values were calculated using the Tukey-Kramer HSD
test. WHO, World Health Organization; ISUP, International Society
of Urologic Pathologists; HSD, honest significant difference.

Figure 2

Comparison of Lamin positive rates
and nuclear grade. (A) Lamin A positive rate (%) vs. Fuhrman grade.
(B) Lamin A positive rate (%) vs. the WHO/ISUP grading system. (C)
Lamin B1 positive rate (%) vs. Fuhrman grade. (D) Lamin B1 positive
rate (%) vs. the WHO/ISUP grading system. (E) Lamin B2 positive
rate (%) vs. Fuhrman grade. (F) Lamin B2 positive rate (%) vs. the
WHO/ISUP grading system. In the box-and-whisker plots, ‘X’
indicates the mean value; horizontal lines represent the median and
interquartile range, and whiskers denote the minimum and maximum
values. P-values were calculated using the Tukey-Kramer HSD test.
WHO, World Health Organization; ISUP, International Society of
Urologic Pathologists; HSD, honest significant difference.

Figure 3

Comparison of Lamin positive rates
and nuclear shape factors. (A-C) Lamin A positive rate vs. nuclear
shape factors: (A) Mean nuclear area, (B) mean nuclear perimeter,
(C) mean nuclear circularity. (D-F) Lamin B1 positive rate vs.
nuclear shape factors: (D) Mean nuclear area, (E) mean nuclear
perimeter, (F) mean nuclear circularity. (G-I) Lamin B2 positive
rate vs. nuclear shape factors: (G) Mean nuclear area, (H) mean
nuclear perimeter, (I) mean nuclear circularity. Straight lines in
the graphs represent regression lines. The correlation coefficient
(R) was calculated using linear regression analysis.

Figure 4

Comparison of nuclear
envelope-associated protein expression and nuclear grade. (A)
Emerin expression vs. Fuhrman grade, (B) SUN1 expression vs.
Fuhrman grade, (C) SUN2 expression vs. Fuhrman grade. (D) Emerin
expression vs. WHO/ISUP grading system, (E) SUN1 expression vs.
WHO/ISUP grading system, (F) SUN2 expression vs. WHO/ISUP grading
system. (G) Nesprin1 expression vs. Fuhrman grade, (H) Nesprin2
expression vs. Fuhrman grade, (I) Nesprin3 expression vs. Fuhrman
grade. (J) Nesprin1 expression vs. WHO/ISUP grading system, (K)
Nesprin2 expression vs. WHO/ISUP grading system, (L) Nesprin3
expression vs. WHO/ISUP grading system. WHO, World Health
Organization; ISUP, International Society of Urologic
Pathologists.

Figure 5

Comparison of SUN1 expression and
nuclear grade. (A) SUN1 expression vs. Fuhrman grade. (B) SUN1
expression vs. WHO/ISUP grading system. WHO, World Health
Organization; ISUP, International Society of Urologic
Pathologists.
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Shibanuma R, Kobayashi S, Konno M, Kaneko R, Nishijima Y, Ikota H, Nomura M, Suzuki K, Yokoo H, Saio M, Saio M, et al: Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma. Oncol Lett 31: 86, 2026.
APA
Shibanuma, R., Kobayashi, S., Konno, M., Kaneko, R., Nishijima, Y., Ikota, H. ... Saio, M. (2026). Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma. Oncology Letters, 31, 86. https://doi.org/10.3892/ol.2025.15439
MLA
Shibanuma, R., Kobayashi, S., Konno, M., Kaneko, R., Nishijima, Y., Ikota, H., Nomura, M., Suzuki, K., Yokoo, H., Saio, M."Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma". Oncology Letters 31.2 (2026): 86.
Chicago
Shibanuma, R., Kobayashi, S., Konno, M., Kaneko, R., Nishijima, Y., Ikota, H., Nomura, M., Suzuki, K., Yokoo, H., Saio, M."Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma". Oncology Letters 31, no. 2 (2026): 86. https://doi.org/10.3892/ol.2025.15439
Copy and paste a formatted citation
x
Spandidos Publications style
Shibanuma R, Kobayashi S, Konno M, Kaneko R, Nishijima Y, Ikota H, Nomura M, Suzuki K, Yokoo H, Saio M, Saio M, et al: Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma. Oncol Lett 31: 86, 2026.
APA
Shibanuma, R., Kobayashi, S., Konno, M., Kaneko, R., Nishijima, Y., Ikota, H. ... Saio, M. (2026). Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma. Oncology Letters, 31, 86. https://doi.org/10.3892/ol.2025.15439
MLA
Shibanuma, R., Kobayashi, S., Konno, M., Kaneko, R., Nishijima, Y., Ikota, H., Nomura, M., Suzuki, K., Yokoo, H., Saio, M."Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma". Oncology Letters 31.2 (2026): 86.
Chicago
Shibanuma, R., Kobayashi, S., Konno, M., Kaneko, R., Nishijima, Y., Ikota, H., Nomura, M., Suzuki, K., Yokoo, H., Saio, M."Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma". Oncology Letters 31, no. 2 (2026): 86. https://doi.org/10.3892/ol.2025.15439
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