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Meningiomlarda STAT3 Ekspresyonu ve Ki-67 ile PHH3 Arasındaki Korelasyon: Rekürrensi Öngörmek Mümkün mü?

Year 2022, Volume: 24 Issue: 2, 201 - 206, 30.08.2022
https://doi.org/10.18678/dtfd.1124225

Abstract

Amaç: Bu çalışmanın amacı meningiom vakalarında PHH3 ile ki-67 proliferasyon indeksi arasındaki korelasyonu incelemek ve STAT3 ekspresyonunun mitotik aktivite, Dünya Sağlık Örgütü 2016 sınıflandırmasına göre derece ve klinikopatolojik özellikler ile ilişkisini değerlendirmektir.
Gereç ve Yöntemler: Düzce Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı arşivlerinden 2012 ve 2021 yılları arasında tanı alan toplam 25 meningiom olgusu çalışmaya dahil edildi. Mitotik figür sayısının en fazla olduğu on büyük büyütme alanından mitotik sayı belirlendi. STAT3, ki-67 ve PHH3 ekspresyonunu belirlemek için formalinle sabitlenmiş, parafine gömülü doku blokları üzerinde immünohistokimyasal çalışma yapıldı. STAT3, boyama yoğunluğuna göre 0 ile 3 puan arasında puanlandı. STAT3 için boyama yüzdeleri, boyanmış hücrelerin manuel sayımı ve toplam tümör hücresi sayısı ile belirlendi. Ki-67 proliferasyon indeksi, manuel sayımla yüzde olarak belirlendi. PHH3 için her bir vakada, 10 büyük büyütme alanından immün boyanmış mitotik figürlerin toplam sayısı değerlendirildi.
Bulgular: STAT3 boyama yüzdesi bakımından tümör dereceleri arasında istatistiksel olarak anlamlı bir farklılık bulundu (p=0,047). Tümör derecesi yüksek olgularda STAT3 ekspresyonu anlamlı olarak daha yüksek idi. Manuel sayım ile en yüksek mitotik indekse sahip olan alanda yüzde olarak hesaplandığında PHH3 ve ki-67 arasında orta derecede pozitif bir korelasyon olduğu bulundu (r=0,621; p=0,001).
Sonuç: Ki-67, PHH3 ve STAT3'ün kombinasyon olarak kullanılması, meningiomların histopatolojik derecelendirilmesinde ve rekürrensi öngörmede faydalı bir yöntem olacaktır.

References

  • Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO classification of tumours of the central nervous system. WHO Classification of Tumours. 4th ed. Lyon: IARC Press; 2016.
  • Olar A. Phosphohistone H3: implications for clinical practice and risk assessment in meningioma. Neuro Oncol. 2015;17(5):631-3.
  • Ozek E, Akdag H, Tosuner Z, Abdallah A, Hatiboglu MA. The correlation between phosphorylated histone H3 (PHH3) and p-STAT3 in meningiomas. Clin Neurol Neurosurg. 2019;178:46-50.
  • Winther TL, Arnli MB, Salvesen Ø, Torp SH. Phosphohistone-H3 proliferation index is superior to mitotic index and MIB-1 expression as a predictor of recurrence in human meningiomas. Am J Clin Pathol. 2016;146(4):510-20.
  • Liu, N, Song SY, Jiang JB, Wang TJ, Yan CX. The prognostic role of Ki-67/MIB-1 in meningioma: A systematic review with meta-analysis. Medicine (Baltimore). 2020;99(9):e18644.
  • Jin C, Huang Y, Nasim M, Yang Y, Lee L. Gastrointestinal stromal tumors risk stratification utilizing phospho-histone H3 evaluated by manual counting and computer-assisted image analysis. Int J Surg Pathol. 2019;27(7):706-12.
  • Hao Q, Dai C, Deng Y, Xu P, Tian T, Shuai Lin S, et al. Pooling analysis on prognostic value of PHH3 expression in cancer patients. Cancer Manag Res. 2018;10:2279-88.
  • Hacking SM, Sajjan S, Lee L, Ziemba Y, Angert M, Yang Y, et al. Potential pitfalls in diagnostic digital image analysis: experience with ki-67 and PHH3 in gastrointestinal neuroendocrine tumors. Pathol Res Pract. 2020;216(3):152753.
  • Kim MJ, Kwon MJ, Kang HS, Choi KC, Nam ES, Cho SJ, et al. Identification of phosphohistone H3 cutoff values corresponding to original WHO grades but distinguishable in well-differentiated gastrointestinal neuroendocrine tumors. Biomed Res Int. 2018;2018:1013640.
  • Huynh J, Chand A, Gough D, Ernst M. Therapeutically exploiting STAT3 activity in cancer - using tissue repair as a road map. Nat Rev Cancer. 2019;19(2):82-96.
  • Setsu N, Kohashi K, Endo M, Yamamoto H, Tamiya S, Takahashi Y, et al. Phosphorylation of signal transducer and activator of transcription 3 in soft tissue leiomyosarcoma is associated with a better prognosis. Int J Cancer. 2013;132(1):109-15.
  • Lee I, Fox PS, Ferguson SD, Bassett R, Kong LY, Schacherer CW, et al. The expression of p-STAT3 in stage IV melanoma: risk of CNS metastasis and survival. Oncotarget. 2012;3(3):336-44.
  • Magrassi L, De-Fraja C, Conti L, Butti G, Infuso L, Govoni S, et al. Expression of the JAK and STAT superfamilies in human meningiomas. J Neurosurg. 1999;91(3):440-6.
  • Chohan MO, Ryan CT, Singh R, Lanning RM, Reiner AS, Rosenblum MK, et al. Predictors of treatment response and survival outcomes in meningioma recurrence with atypical or anaplastic histology. Neurosurgery. 2018;82(6):824-32.
  • Delgado-López PD, Cubo-Delgado E, González-Bernal JJ, Martín-Alonso J. A practical overview on the molecular biology of meningioma. Curr Neurol Neurosci Rep. 2020;20(12):62.
  • Johnson M, O'Connell M, Walter K. STAT3 activation and risk of recurrence in meningiomas. Oncol Lett. 2017;13(4):2432-6.
  • Paldor I, Awad M, Sufaro YZ, Kaye AH, Shoshan Y. Review of controversies in management of non-benign meningioma. J Clin Neurosci. 2016;31:37-46.
  • Nowosielski M, Galldiks N, Iglseder S, Kickingereder P, von Deimling A, Bendszus M, et al. Diagnostic challenges in meningioma. Neuro Oncol. 2017;19(12):1588-98.
  • Parada CA, Osbun J, Kaur S, Yakkioui Y, Shi M, Pan C, et al. Kinome and phosphoproteome of high-grade meningiomas reveal AKAP12 as a central regulator of aggressiveness and its possible role in progression. Sci Rep. 2018;8(1):2098.
  • Johnson MD, O'Connell M, Facik M, Maurer P, Jahromi B, Pilcher W. Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3. J Neurooncol. 2012;107(1):121-31.
  • Valle-Mendiola A, Soto-Cruz I. Energy metabolism in cancer: the roles of STAT3 and STAT5 in the regulation of metabolism-related genes. Cancers (Basel). 2020;12(1):124.
  • Page BD, Ball DP, Gunning PT. Signal transducer and activator of transcription 3 inhibitors: a patent review. Expert Opin Ther Pat. 2011;21(1):65-83.
  • Igelmann S, Neubauer HA, Ferbeyre G. STAT3 and STAT5 activation in solid cancers. Cancers (Basel). 2019;11(10):1428.
  • Johnson MD, O'Connell M, Vito F, Bakos RS. Increased STAT-3 and synchronous activation of Raf-1-MEK-1-MAPK, and phosphatidylinositol 3-Kinase-Akt-mTOR pathways in atypical and anaplastic meningiomas. J Neurooncol. 2009;92(2):129-36.
  • Cree IA, Tan PH, Travis WD, Wesseling P, Yagi Y, White VA, et al. Counting mitoses: SI(ze) matters! Mod Pathol. 2021;34(9):1651-7.
  • Kim YJ, Ketter R, Steudel WI, Feiden W. Prognostic significance of the mitotic index using the mitosis marker anti-phosphohistone H3 in meningiomas. Am J Clin Pathol. 2007;128(1):118-25.
  • Elmaci I, Altinoz MA, Sari R, Bolukbasi FH. Phosphorylated histone H3 (PHH3) as a novel cell proliferation marker and prognosticator for meningeal tumors: A short review. Appl Immunohistochem Mol Morphol. 2018;26(9):627-31.
  • Nagahama A, Yashiro M, Kawashima T, Nakajo K, Morisako H, Uda T, et al. Combination of p53 and Ki67 as a promising predictor of postoperative recurrence of meningioma. Anticancer Res. 2021;41(1):203-10.
  • Puripat N, Loharamtaweethong K. Phosphohistone H3 (PHH3) as a surrogate of mitotic figure count for grading in meningiomas: a comparison of PHH3 (S10) versus PHH3 (S28) antibodies. Virchows Arch. 2019;474(1):87-96.
  • Fukushima S, Terasaki M, Sakata K, Miyagi N, Kato S, Sugita Y, et al. Sensitivity and usefulness of anti-phosphohistone-H3 antibody immunostaining for counting mitotic figures in meningioma cases. Brain Tumor Pathol. 2009;26(2):51-7.

STAT3 Expression and Correlation Between Ki-67 and PHH3 in Meningiomas: Is it Possible to Predict Recurrence?

Year 2022, Volume: 24 Issue: 2, 201 - 206, 30.08.2022
https://doi.org/10.18678/dtfd.1124225

Abstract

Aim: The aim of this study was to investigate the correlation between PHH3 and ki-67 labeling index, and the association of STAT3 expression with mitotic index, grade by World Health Organization 2016 classification, and clinicopathological features of meningioma cases.
Material and Methods: A total of 25 meningioma cases from the archives of the Department of Pathology, Düzce University School of Medicine, diagnosed between 2012 and 2021 were included in the study. The mitotic count from the ten fields with the highest number of mitotic figures was determined. Immunohistochemistry was performed on the formalin-fixed, paraffin-embedded tissue blocks to determine STAT3, ki-67, and PHH3 expression. STAT3 was scored between 0 and 3 points according to staining intensity. Staining percentages for STAT3 were determined using a manual count of stained cells and the total number of tumor cells. The ki-67 labeling index was determined as a percentage by a manual count. For PHH3, the total number of immunostained mitotic figures per 10 high-power fields were evaluated in each case.
Results: A statistically significant difference was found in terms of the percentage of STAT3 staining between the tumor grades (p=0.047). STAT3 expression was significantly higher in cases with high tumor grades. A moderate positive correlation was found between ki-67 and PHH3 when calculated as a percentage in the area with the highest mitotic index by manual counting (r=0.621, p=0.001).
Conclusion: A combination of ki-67, PHH3, and STAT3 will be useful in the grading of meningiomas and predict the recurrence.

References

  • Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO classification of tumours of the central nervous system. WHO Classification of Tumours. 4th ed. Lyon: IARC Press; 2016.
  • Olar A. Phosphohistone H3: implications for clinical practice and risk assessment in meningioma. Neuro Oncol. 2015;17(5):631-3.
  • Ozek E, Akdag H, Tosuner Z, Abdallah A, Hatiboglu MA. The correlation between phosphorylated histone H3 (PHH3) and p-STAT3 in meningiomas. Clin Neurol Neurosurg. 2019;178:46-50.
  • Winther TL, Arnli MB, Salvesen Ø, Torp SH. Phosphohistone-H3 proliferation index is superior to mitotic index and MIB-1 expression as a predictor of recurrence in human meningiomas. Am J Clin Pathol. 2016;146(4):510-20.
  • Liu, N, Song SY, Jiang JB, Wang TJ, Yan CX. The prognostic role of Ki-67/MIB-1 in meningioma: A systematic review with meta-analysis. Medicine (Baltimore). 2020;99(9):e18644.
  • Jin C, Huang Y, Nasim M, Yang Y, Lee L. Gastrointestinal stromal tumors risk stratification utilizing phospho-histone H3 evaluated by manual counting and computer-assisted image analysis. Int J Surg Pathol. 2019;27(7):706-12.
  • Hao Q, Dai C, Deng Y, Xu P, Tian T, Shuai Lin S, et al. Pooling analysis on prognostic value of PHH3 expression in cancer patients. Cancer Manag Res. 2018;10:2279-88.
  • Hacking SM, Sajjan S, Lee L, Ziemba Y, Angert M, Yang Y, et al. Potential pitfalls in diagnostic digital image analysis: experience with ki-67 and PHH3 in gastrointestinal neuroendocrine tumors. Pathol Res Pract. 2020;216(3):152753.
  • Kim MJ, Kwon MJ, Kang HS, Choi KC, Nam ES, Cho SJ, et al. Identification of phosphohistone H3 cutoff values corresponding to original WHO grades but distinguishable in well-differentiated gastrointestinal neuroendocrine tumors. Biomed Res Int. 2018;2018:1013640.
  • Huynh J, Chand A, Gough D, Ernst M. Therapeutically exploiting STAT3 activity in cancer - using tissue repair as a road map. Nat Rev Cancer. 2019;19(2):82-96.
  • Setsu N, Kohashi K, Endo M, Yamamoto H, Tamiya S, Takahashi Y, et al. Phosphorylation of signal transducer and activator of transcription 3 in soft tissue leiomyosarcoma is associated with a better prognosis. Int J Cancer. 2013;132(1):109-15.
  • Lee I, Fox PS, Ferguson SD, Bassett R, Kong LY, Schacherer CW, et al. The expression of p-STAT3 in stage IV melanoma: risk of CNS metastasis and survival. Oncotarget. 2012;3(3):336-44.
  • Magrassi L, De-Fraja C, Conti L, Butti G, Infuso L, Govoni S, et al. Expression of the JAK and STAT superfamilies in human meningiomas. J Neurosurg. 1999;91(3):440-6.
  • Chohan MO, Ryan CT, Singh R, Lanning RM, Reiner AS, Rosenblum MK, et al. Predictors of treatment response and survival outcomes in meningioma recurrence with atypical or anaplastic histology. Neurosurgery. 2018;82(6):824-32.
  • Delgado-López PD, Cubo-Delgado E, González-Bernal JJ, Martín-Alonso J. A practical overview on the molecular biology of meningioma. Curr Neurol Neurosci Rep. 2020;20(12):62.
  • Johnson M, O'Connell M, Walter K. STAT3 activation and risk of recurrence in meningiomas. Oncol Lett. 2017;13(4):2432-6.
  • Paldor I, Awad M, Sufaro YZ, Kaye AH, Shoshan Y. Review of controversies in management of non-benign meningioma. J Clin Neurosci. 2016;31:37-46.
  • Nowosielski M, Galldiks N, Iglseder S, Kickingereder P, von Deimling A, Bendszus M, et al. Diagnostic challenges in meningioma. Neuro Oncol. 2017;19(12):1588-98.
  • Parada CA, Osbun J, Kaur S, Yakkioui Y, Shi M, Pan C, et al. Kinome and phosphoproteome of high-grade meningiomas reveal AKAP12 as a central regulator of aggressiveness and its possible role in progression. Sci Rep. 2018;8(1):2098.
  • Johnson MD, O'Connell M, Facik M, Maurer P, Jahromi B, Pilcher W. Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3. J Neurooncol. 2012;107(1):121-31.
  • Valle-Mendiola A, Soto-Cruz I. Energy metabolism in cancer: the roles of STAT3 and STAT5 in the regulation of metabolism-related genes. Cancers (Basel). 2020;12(1):124.
  • Page BD, Ball DP, Gunning PT. Signal transducer and activator of transcription 3 inhibitors: a patent review. Expert Opin Ther Pat. 2011;21(1):65-83.
  • Igelmann S, Neubauer HA, Ferbeyre G. STAT3 and STAT5 activation in solid cancers. Cancers (Basel). 2019;11(10):1428.
  • Johnson MD, O'Connell M, Vito F, Bakos RS. Increased STAT-3 and synchronous activation of Raf-1-MEK-1-MAPK, and phosphatidylinositol 3-Kinase-Akt-mTOR pathways in atypical and anaplastic meningiomas. J Neurooncol. 2009;92(2):129-36.
  • Cree IA, Tan PH, Travis WD, Wesseling P, Yagi Y, White VA, et al. Counting mitoses: SI(ze) matters! Mod Pathol. 2021;34(9):1651-7.
  • Kim YJ, Ketter R, Steudel WI, Feiden W. Prognostic significance of the mitotic index using the mitosis marker anti-phosphohistone H3 in meningiomas. Am J Clin Pathol. 2007;128(1):118-25.
  • Elmaci I, Altinoz MA, Sari R, Bolukbasi FH. Phosphorylated histone H3 (PHH3) as a novel cell proliferation marker and prognosticator for meningeal tumors: A short review. Appl Immunohistochem Mol Morphol. 2018;26(9):627-31.
  • Nagahama A, Yashiro M, Kawashima T, Nakajo K, Morisako H, Uda T, et al. Combination of p53 and Ki67 as a promising predictor of postoperative recurrence of meningioma. Anticancer Res. 2021;41(1):203-10.
  • Puripat N, Loharamtaweethong K. Phosphohistone H3 (PHH3) as a surrogate of mitotic figure count for grading in meningiomas: a comparison of PHH3 (S10) versus PHH3 (S28) antibodies. Virchows Arch. 2019;474(1):87-96.
  • Fukushima S, Terasaki M, Sakata K, Miyagi N, Kato S, Sugita Y, et al. Sensitivity and usefulness of anti-phosphohistone-H3 antibody immunostaining for counting mitotic figures in meningioma cases. Brain Tumor Pathol. 2009;26(2):51-7.
There are 30 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Sinem Kantarcıoğlu Coşkun 0000-0002-8133-8665

Güven Kılıç 0000-0001-5050-7908

Publication Date August 30, 2022
Submission Date May 31, 2022
Published in Issue Year 2022 Volume: 24 Issue: 2

Cite

APA Kantarcıoğlu Coşkun, S., & Kılıç, G. (2022). STAT3 Expression and Correlation Between Ki-67 and PHH3 in Meningiomas: Is it Possible to Predict Recurrence?. Duzce Medical Journal, 24(2), 201-206. https://doi.org/10.18678/dtfd.1124225
AMA Kantarcıoğlu Coşkun S, Kılıç G. STAT3 Expression and Correlation Between Ki-67 and PHH3 in Meningiomas: Is it Possible to Predict Recurrence?. Duzce Med J. August 2022;24(2):201-206. doi:10.18678/dtfd.1124225
Chicago Kantarcıoğlu Coşkun, Sinem, and Güven Kılıç. “STAT3 Expression and Correlation Between Ki-67 and PHH3 in Meningiomas: Is It Possible to Predict Recurrence?”. Duzce Medical Journal 24, no. 2 (August 2022): 201-6. https://doi.org/10.18678/dtfd.1124225.
EndNote Kantarcıoğlu Coşkun S, Kılıç G (August 1, 2022) STAT3 Expression and Correlation Between Ki-67 and PHH3 in Meningiomas: Is it Possible to Predict Recurrence?. Duzce Medical Journal 24 2 201–206.
IEEE S. Kantarcıoğlu Coşkun and G. Kılıç, “STAT3 Expression and Correlation Between Ki-67 and PHH3 in Meningiomas: Is it Possible to Predict Recurrence?”, Duzce Med J, vol. 24, no. 2, pp. 201–206, 2022, doi: 10.18678/dtfd.1124225.
ISNAD Kantarcıoğlu Coşkun, Sinem - Kılıç, Güven. “STAT3 Expression and Correlation Between Ki-67 and PHH3 in Meningiomas: Is It Possible to Predict Recurrence?”. Duzce Medical Journal 24/2 (August 2022), 201-206. https://doi.org/10.18678/dtfd.1124225.
JAMA Kantarcıoğlu Coşkun S, Kılıç G. STAT3 Expression and Correlation Between Ki-67 and PHH3 in Meningiomas: Is it Possible to Predict Recurrence?. Duzce Med J. 2022;24:201–206.
MLA Kantarcıoğlu Coşkun, Sinem and Güven Kılıç. “STAT3 Expression and Correlation Between Ki-67 and PHH3 in Meningiomas: Is It Possible to Predict Recurrence?”. Duzce Medical Journal, vol. 24, no. 2, 2022, pp. 201-6, doi:10.18678/dtfd.1124225.
Vancouver Kantarcıoğlu Coşkun S, Kılıç G. STAT3 Expression and Correlation Between Ki-67 and PHH3 in Meningiomas: Is it Possible to Predict Recurrence?. Duzce Med J. 2022;24(2):201-6.