Study of Immunohistochemical Profile Of Pten And Ppar-Γ in the Histomorphological Spectrum of Renal Cell Carcinoma

Keywords: immunohistochemistry, peroxisome proliferator activated receptor gamma, phosphatase and tensin homolog, prognostic makers, renal cell carcinoma

Introduction: Renal cell carcinoma (RCC) has a late presentation and is highly therapy resistant.[1],[2] Phosphatase and tensin homolog (PTEN) and peroxisome proliferator activated receptor gamma (PPAR-γ) have been implicated in RCC as tumor suppressors, with limited studies for PPAR-γ.[3],[4] PPAR-γ agonists have an additive effect when combined with chemotherapy, in certain malignancies.[5] ims: Our study aimed to evaluate the association between PTEN and PPAR-γ immunohistochemical expression and the histomorphological parameters of RCC.

Methodology: This prospective observational study was conducted from October 2022 to July 2024, on 48 histopathologically confirmed RCC cases. Immunohistochemical analysis was done on formalin fixed paraffin embedded tissues, and PTEN and PPAR-γ primary monoclonal antibodies (Clone 6H2.1 and K.242.9 respectively) were used. Scoring was done based on percentage and intensity of stained tumor cells, and categories assigned.[6] H-score was also calculated, due to heterogeneity in staining.[7] P value less than .05 was considered significant.

Results: The 48 RCC patients had a mean age of 55.46 years, with clear cell comprising the majority (31 cases, 64.58%). 40 cases were gradable, with 15 belonging to World Health Organization/ International Society of Urological Pathology (WHO/ISUP) grade 2. Pathological tumor (pT) stage pT3a was noted in 20 cases. PTEN loss was encountered in 17 cases and PPAR-γ loss in 15 cases. Loss of expression of both markers showed significant association with revised WHO/ISUP grade, pT stage and Leibovich prognostic model. In addition, PTEN loss was significantly associated with sarcomatoid differentiation, while PPAR-γ loss was associated with rhabdoid features. There was a significant positive correlation between PTEN and PPAR-γ expression levels. H-score cut-off values of 40 for PTEN and 35 for PPAR-γ were associated with poor prognosis.

Conclusion: PTEN and PPAR-γ immunohistochemical assessment is important in RCC with unfavorable histopathological parameters. It forms a basis for molecular workup, essential for precision therapy.

Digital Formats:

Figure 1: PTEN focal moderate cytoplasmic positivity with H-score 40, 20x

Figure 2: Kaplan-Meier curve of cancer-specific survival of RCC patients with PPAR-γ H-score   ≤ 35 versus score > 35

References:
[1] Porta C. et al. (2019) Nature Reviews Nephrology, 15(7), 423-33. 

[2] Fernandez-Pello S. et al. (2017) European urology. 71(3), 426-36.

[3] Tang L. et al. (2017) PLoS One, 12(7), e0179437.

[4] Wu Y. et al. (2019) DNA and cell biology, 38(7), 700-7.

[5] Xu Y. et al. (2020) PPAR research, 2020.

[6]Zhu C. et al. (2015) International journal of clinical and experimental pathology, 8(10), 12668-77.

[7] Pallares J. et al. (2005) Modern pathology, 18(5), 719-27.

Biography: Dr. Debaditya Haldar has completed his M.D. in Pathology from Indira Gandhi Institute of Medical Sciences Patna, Bihar, India. A resident of Kolkata, West Bengal, he worked as Chief of Lab in Dr. Lal Path Labs post his M.D., and is currently pursuing D.M. in Oncopathology at Kidwai Memorial Institute of Oncology, Bangalore. His area of interest lies in uropathology and neuropathology, and till date, he has published twelve articles in various journals, and attended many state level and national conferences. He has a keen interest in research, and loves reading and educating others.

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