Immunohistochemical features of gastrointestinal stromal tumors and their role for differential diagnosis and prognosis

Keywords: CD117, DOG-1, CD56, spindled GISTs, epithelioid GISTs, prognostic markers, p16ink4A, Ki-67

Abstract

The aim. To clarify all most important immunohistochemical features of gastrointestinal stromal tumors with different histological patterns and analyze the role of expression of Ki-67, MMP-9, VEGF and p16ink4A as a predictive markers of tumor progression.

Materials and methods. The study is based on analysis of 100 primary GISTs for description of their morphological features and 36 GISTs taken from this 100 for study of prognostic markers.

Results. All spindle cell GISTs have shown diffuse expression of CD117 in tumor cells. The levels of CD117 expression varied from strong expression (3+) until mild expression (1+). Strong expression were seen in 75,8 % of spindle cell GISTs. Epithelioid GISTs demonstrated heterognous moderate or mild expression of CD117. All primary epithelioid GISTs from patients that had relapse of tumor in period from 1 till 3 years demonstrated focal mild expression of CD 117 in tumor cells. Expression of DOG-1 were seen in all 100 cases of GISTs, that were included in our study. The strong expression of DOG-1 (3+) were seen in all 45 GISTs that had low mitotic rate (≤5 mitoses per 50HPF) and not associated with their histological pattern. GISTs with high mitotic rate demonstrated heterogeneous expression of DOG-1 in tumors: moderate expression (2+) with patchy areas of strong expression (3+). Expression of CD56 was not found in spindle cell GISTs, but single tumor cells of epithelioid GISTs that had high mitotic rate demonstrated expression of this marker. The average expression of p16ink4A were higher in tumors that gave relapses compared with tumors without relapses (50,3 % versus 5,7 % respectively, U-test=16.5; p≤0,01).The average expression of MMP-9 also were significantly higher in GISTs that gave relapses: 63,2 % compared with 13,4 % in GISTs without relapse (U-test=16; p≤0 ,01).The strong VEGF expression was found in 66,7 % of GISTs that had relapses and only in 8,3 % of GISTs without relapses. 50 % of GISTs without relapses was negative for VEGF. Finally, the average expression of Ki-67 were 13,4 % in GISTs with relapses and 8,7 % in GISTs without them (U-test=16; p≤0,01).

Conclusion. We highly recommend using DOG-1 for epithelioid GISTs. Additionally in epithelioid GISTs can be used CD56 that can give focal positive reaction in some tumour cells. The following minimal panel of markers for differential diagnosis of spindled GISTs from other mesenchymal tumors of gastrointestinal tract is proposed: CD117, DOG-1 and SMA, where the first too markers will demonstrated the moderate or strong diffuse expression and SMA can be occasionally positive in some tumor cells. p16ink4A, ki-67, VEGF and MMP-9 can be used as additional prognostic markers in GISTs.

Downloads

Download data is not yet available.

Author Biography

Yana Miroshnichenko, Kharkiv Medical Academy of Postgraduate Education

Department of Pathological Anatomy

References

Lokuhetty, D. (2019). Gastrointestinal stromal tumour. WHO Classification of Tumours: Digestive System Tumours. Lyon, 439–443.

SEER Inquiry System – View (2011). National Cancer Institute: Surveillance, Epidemiology, and End Result Program. Available at: https://seer.cancer.gov/seerinquiry/index.php?page=view&id=20100014&type=q

Gupta, A., Suri, V., Goyal, N., Chhabra, S., Garg, A., Bhati, G., Kaur, J. (2020). Histomorphological spectrum of gastrointestinal stromal tumors – An institutional experience in a series of seven cases. Adesh University Journal of Medical Sciences & Research, 2, 112–116. doi: http://doi.org/10.25259/aujmsr_33_2020

Ceausu, M., Socea, B., Ciobotaru, V., Constantin, V., Enache, S., Enache, V. et. al. (2021). A multidisciplinary approach in the diagnostic challenge of GIST. Experimental and Therapeutic Medicine, 22 (4). doi: http://doi.org/10.3892/etm.2021.10497

Hirota, S. (2018). Differential diagnosis of gastrointestinal stromal tumor by histopathology and immunohistochemistry. Translational Gastroenterology and Hepatology, 3, 27–27. doi: http://doi.org/10.21037/tgh.2018.04.01

Gastrointestinal Stromal Tumor (GIST). Differential Diagnosis. Surgical Pathology Criteria. Stanford University School of Medicine. Available at: http://surgpathcriteria.stanford.edu/gitumors/gist-gastrointestinal-stromal-tumor/differential-diagnosis.html

Gheorghe, G., Bacalbasa, N., Ceobanu, G., Ilie, M., Enache, V., Constantinescu, G. et. al. (2021). Gastrointestinal Stromal Tumors – A Mini Review. Journal of Personalized Medicine, 11 (8), 694. doi: http://doi.org/10.3390/jpm11080694

Zhao, W. Y., Xu, J., Wang, M., Zhang, Z. Z., Tu, L., Wang, C. J. et. al. (2014). Prognostic value of Ki67 index in gastrointestinal stromal tumors. International journal of clinical and experimental pathology, 7 (5), 2298–2304.

Xu, D., Su, C., Guo, L., Yan, H., Wang, S., Yuan, C. et. al. 2019). Predictive significance of serum MMP-9 in papillary thyroid carcinoma. Open Life Sciences, 14 (1), 275–287. doi: http://doi.org/10.1515/biol-2019-0031

Liu, N., Huang, J., Sun, S., Zhou, Z., Zhang, J., Gao, F., Sun, Q. (2015). Expression of matrix metalloproteinase-9, cyclooxygenase-2 and vascular endothelial growth factor are increased in gastrointestinal stromal tumors. International journal of clinical and experimental medicine, 8 (4), 6495–6501.

Inoue, K., A. Fry, E. (2018). Aberrant expression of p16INK4a in human cancers – a new biomarker? Cancer Reports and Reviews, 2 (2). doi: http://doi.org/10.15761/crr.1000145

Laurini, J. A., Blanke, C. D., Cooper, K., Demetri, G. D., Dematteo, R. P., Fletcher, C. D. M. (2019). Protocol for the Examination of Biopsy Specimens From Patients With Gastrointestinal Stromal Tumor (GIST). College of American pathologists. Available at: https://documents.cap.org/protocols/cp-other-gist-biopsy-19-4100.pdf

Fletcher, C. D. M., Berman, J. J., Corless, C., Gorstein, F., Lasota, J., Longley, B. J. et. al. (2002). Diagnosis of gastrointestinal stromal tumors: A consensus approach. Human Pathology, 33 (5), 459–465. doi: http://doi.org/10.1053/hupa.2002.123545

Mei, L., Smith, S. C., Faber, A. C., Trent, J., Grossman, S. R., Stratakis, C. A., Boikos, S. A. (2018). Gastrointestinal Stromal Tumors: The GIST of Precision Medicine. Trends in Cancer, 4 (1), 74–91. doi: http://doi.org/10.1016/j.trecan.2017.11.006

Agaimy, A., Wünsch, P. H. (2007). Distribution of neural cell adhesion molecule (NCAM/CD56) in gastrointestinal stromal tumours and their intra-abdominal mesenchymal mimics. Journal of Clinical Pathology, 61 (4), 499–503. doi: http://doi.org/10.1136/jcp.2007.052696

Miettinen, M., Wang, Z.-F., Lasota, J. (2009). DOG1 Antibody in the Differential Diagnosis of Gastrointestinal Stromal Tumors. American Journal of Surgical Pathology, 33(9), 1401–1408. doi: http://doi.org/10.1097/pas.0b013e3181a90e1a

Kiśluk, J., Zińczuk, J., Kemona, A., Guzińska-Ustymowicz, K., Żurawska, J., Kędra, B. (2016). Expression of CD117, DOG-1, and IGF-1R in gastrointestinal stromal tumours – an analysis of 70 cases from 2004 to 2010. Gastroenterology Review, 2, 115–122. doi: http://doi.org/10.5114/pg.2015.52587

Swalchick, W., Shamekh, R., Bui, M. M. (2015). Is DOG1 Immunoreactivity Specific to Gastrointestinal Stromal Tumor? Cancer Control, 22 (4), 498–504. doi: http://doi.org/10.1177/107327481502200416

Meena, R. K., Koshti, A., R.K., N., Malik, R., Junwal, A. (2020). Expression of Vimentin, Desmin, CD34 and S100 in Malignant Soft Tissue Tumours in a Study Conducted in Central India. Journal of Evolution of Medical and Dental Sciences, 9 (52), 3977–3981. doi: http://doi.org/10.14260/jemds/2020/869

Haller, F., Agaimy, A., Cameron, S., Beyer, M., Gunawan, B., Happel, N. et. al. (2010). Expression of p16INK4Ain gastrointestinal stromal tumours (GISTs): two different forms exist that independently correlate with poor prognosis. Histopathology, 56 (3), 305–318. doi: http://doi.org/10.1111/j.1365-2559.2010.03478.x

Mendaza, S., Fernández-Irigoyen, J., Santamaría, E., Zudaire, T., Guarch, R., Guerrero-Setas, D. et. al. (2020). Absence of Nuclear p16 Is a Diagnostic and Independent Prognostic Biomarker in Squamous Cell Carcinoma of the Cervix. International Journal of Molecular Sciences, 21 (6), 2125. doi: http://doi.org/10.3390/ijms21062125


👁 101
⬇ 108
Published
2021-11-30
How to Cite
Miroshnichenko, Y. (2021). Immunohistochemical features of gastrointestinal stromal tumors and their role for differential diagnosis and prognosis. EUREKA: Health Sciences, (6), 10-16. https://doi.org/10.21303/2504-5679.2021.002183
Section
Medicine and Dentistry