Abstract
Amaç: Endometrial karsinomların prognozunu anlayabilmek ve tedavilerini belirleyebilmek için endometrium karsinomlarında mikrosatellit
instabiliteyi (MSI) değerlendirmek ve tümörün moleküler profilini anlayabilmek her geçen gün daha önemli bir hal almaktadır. Biz de çalışmamızda
son iki yıl içerisinde MSI durumu immünhistokimyasal ve moleküler olarak araştırılan hastalarda morfolojik parametreleri araştırmayı amaçladık.
Gereç ve Yöntem: Mikrosatellit stabilite durumu araştırılan 43 endometrium karsinomu hastası çalışmaya dahil edilmiştir. Hasta yaşı, tümör boyutu
ve tümör lokalizasyonu, gönderilen materyalin tipi ve rezeksiyon materyali ise TNM evresi, immünohistokimyasal boyama sonuçları ve yapıldı ise
sekanslama analiz sonuçları patoloji raporlarından elde edilmiş ve kaydedilmiştir. Hastalara ait H&E boyalı camlar arşivden çıkarılarak retrospektif
olarak tekrar değerlendirilmiş; intratümöral ve peritümöral iltihabi hücre infiltrasyonu varlığı, lenfovasküler ve perinöral invazyon varlığı incelenerek
kaydedilmiştir.
Bulgular: MSS olguların hepsinde peritümöral ve intratümöral enflamatuvar hücre yanıtı hafif düzeyde (+1) saptanmış, MSI grupta ise peritümöral
enflamatuvar yanıt 5 (%28) tümörde hafif (+1), 11 (%61) tümörde orta (+2) ve 2 (%11) tümörde şiddetli (+3) olarak tespit edilmiştir. İntratümöral
enflamasyon 3 (%17) tümörde hafif (+1) düzeyde iken 8 (%44) tümörde orta (+2) ve 7 (%39) tümörde de şiddetli (+3) düzeyde saptanmıştır. Hem
peritümöral enflamasyon hem de intratümöral enflamasyon açısından iki grup arasında istatistiksel olarak anlamlı fark elde edilmiştir (p<0,05 ve
p<0,001).
Sonuç: MSI grupta hem intratümöral hem de peritümöral iltihabi hücre yoğunluğu, literatür ile benzer olacak şekilde, MSS gruba oranla yüksek
bulunmuştur (sırasıyla p<0,001 ve p<0,05). Literatürdeki birçok çalışma göstermiştir ki d-MMR veya MSI-H grup tümörler PD-1 inhibisyonu
tedavilerine çok daha iyi yanıt vermektedir. Bu durum, MSS ve d-MMR grubu tümörlere göre daha kötü prognozlu olduğu bilinen bu grup tümörler
için bir tedavi umudu oluşturmaktadır. Histomorfolojik değerlendirme ile saptanan intratümöral ve peritümöral iltihabi hücre yoğunluğu, bu grup
hastayı mikrosatellit inceleme yapma endikasyonu açısından uyarıcı nitelikte kabul edilebilir.
Ethical Statement
Retrospektif bir çalışma olduğu için insan ve hayvan deneyi içermemektedir. Bu nedenle onay alınmamıştır
Supporting Institution
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Project Number
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Thanks
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References
- 1. Bell DW, Ellenson LH. Molecular Genetics of Endometrial Carcinoma. Annu Rev Pathol. 2019;14:339-367.
- 2. Zhao S, Chen L, Zang Y, et al. Endometrial cancer in Lynch syndrome. Int J Cancer. 2022;150:7-17.
- 3. Yang G, Zheng RY, Jin ZS. Correlations between microsatellite instability and the biological behaviour of tumours. J Cancer Res Clin Oncol. 2019;145:2891-2899.
- 4. Olave MC, Graham RP. Mismatch repair deficiency: The what, how and why it is important. Genes Chromosomes Cancer. 2022;61:314-321.
- 5. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15:10-17.
- 6. Vermij L, Smit V, Nout R, Bosse T. Incorporation of molecular characteristics into endometrial cancer management. Histopathology. 2020;76:52-63.
- 7. Stinton C, Fraser H, Al-Khudairy L, et al. Testing for lynch syndrome in people with endometrial cancer using immunohistochemistry and microsatellite instability-based testing strategies - A systematic review of test accuracy. Gynecol Oncol. 2021;160:148-160.
- 8. Hussein YR, Soslow RA. Molecular insights into the classification of highgrade endometrial carcinoma. Pathology. 2018;50:151-161.
- 9. Wadee R, Grayson W. A potpourri of pathogenetic pathways in endometrial carcinoma with a focus on Lynch Syndrome. Ann Diagn Pathol. 2019;39:92-104.
- 10. Kurnit KC, Westin SN, Coleman RL. Microsatellite instability in endometrial cancer: New purpose for an old test. Cancer. 2019;125:2154-2163.
- 11. Brooks RA, Fleming GF, Lastra RR, et al. Current recommendations and recent progress in endometrial cancer. CA Cancer J Clin. 2019;69:258-279.
- 12. Kahn RM, Gordhandas S, Maddy BP, et al. Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population? Cancer. 2019;125:3172-3183.
Abstract
Objectives: To understand the prognosis of endometrial carcinomas and determine their treatment, it is becoming increasingly important to
evaluate microsatellite instability (MSI) in endometrial carcinomas and to understand the molecular profile of the tumors. So, in our study, we
aimed to determine morphological parameters in patients whose MSI status was investigated immunohistochemically and molecularly in the last
two years.
Materials and Methods: Forty-three patients with endometrial carcinoma, whose microsatellite stability was investigated, were included in the
study. Patient age, tumor size and tumor localization, type of material sent and resection material, TNM stage, immunohistochemical staining
results and sequencing analysis results, if performed, were obtained from pathology reports and recorded. The H&E stained glasses of the patients
were removed from the archive and reevaluated retrospectively. The presence of intratumoral and peritumoral inflammatory cell infiltration,
lymphovascular and perineural invasion were examined and recorded.
Results: Peritumoral and intratumoral inflammatory cell response was found to be mild (+1) in all MSS cases. In the MSI group, the peritumoral
inflammatory response was mild (+1) in 5 (28%) tumors, moderate (+2) in 11 (61%) tumors, and severe (+3) in 2 (11%) tumors. Intratumoral
inflammation was mild (+1) in 3 (17%) tumors, moderate (+2) in 8 (44%) tumors, and severe (+3) in 7 (39%) tumors. There was a statistically
significant difference between the two groups in terms of both peritumoral and intratumoral inflammation (p<0.05 and p<0.001).
Conclusion: In the MSI group, both intratumoral and peritumoral inflammatory cell densities were found to be higher than in the MSS group,
similar to the literature (p<0.001 and p<0.05, respectively). Many studies in the literature have shown that d-MMR or MSI-H group tumors respond
much better to PD-1 inhibition treatments. This creates a treatment choice for this group of tumors, which are known to have a worse prognosis
than MSS and d-MMR group tumors.
Ethical Statement
-
Supporting Institution
-
Project Number
-
Thanks
-
References
- 1. Bell DW, Ellenson LH. Molecular Genetics of Endometrial Carcinoma. Annu Rev Pathol. 2019;14:339-367.
- 2. Zhao S, Chen L, Zang Y, et al. Endometrial cancer in Lynch syndrome. Int J Cancer. 2022;150:7-17.
- 3. Yang G, Zheng RY, Jin ZS. Correlations between microsatellite instability and the biological behaviour of tumours. J Cancer Res Clin Oncol. 2019;145:2891-2899.
- 4. Olave MC, Graham RP. Mismatch repair deficiency: The what, how and why it is important. Genes Chromosomes Cancer. 2022;61:314-321.
- 5. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15:10-17.
- 6. Vermij L, Smit V, Nout R, Bosse T. Incorporation of molecular characteristics into endometrial cancer management. Histopathology. 2020;76:52-63.
- 7. Stinton C, Fraser H, Al-Khudairy L, et al. Testing for lynch syndrome in people with endometrial cancer using immunohistochemistry and microsatellite instability-based testing strategies - A systematic review of test accuracy. Gynecol Oncol. 2021;160:148-160.
- 8. Hussein YR, Soslow RA. Molecular insights into the classification of highgrade endometrial carcinoma. Pathology. 2018;50:151-161.
- 9. Wadee R, Grayson W. A potpourri of pathogenetic pathways in endometrial carcinoma with a focus on Lynch Syndrome. Ann Diagn Pathol. 2019;39:92-104.
- 10. Kurnit KC, Westin SN, Coleman RL. Microsatellite instability in endometrial cancer: New purpose for an old test. Cancer. 2019;125:2154-2163.
- 11. Brooks RA, Fleming GF, Lastra RR, et al. Current recommendations and recent progress in endometrial cancer. CA Cancer J Clin. 2019;69:258-279.
- 12. Kahn RM, Gordhandas S, Maddy BP, et al. Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population? Cancer. 2019;125:3172-3183.
Details
| Primary Language | English |
|---|---|
| Subjects | Pathology |
| Journal Section | Articles |
| Authors | |
| Project Number | - |
| Publication Date | October 18, 2022 |
| Published in Issue | Year 2022 Volume: 75 Issue: 3 |
