Is there any difference between endometrial hyperplasia and endometrial carcinoma in terms of expression of TRPM2 and TRPM7 ion channels?

Is there any difference between endometrial hyperplasia and endometrial carcinoma in terms of expression of TRPM2 and TRPM7 ion channels?

Background/aim: This study compared TRPM2 and TRPM7 ion channel gene expression and immunohistochemical staining inendometrial hyperplasia and endometrium adenocarcinoma.Materials and methods: Sections were taken from paraffin blocks of 120 patients who were divided into 6 groups as follows: G1 (n =20), proliferative endometrium (PE); G2 (n = 20), EH without atypia; G3 (n = 20), EH with atypia; G4 (n = 20), stage 1A, grade 1 EC;G5 (n = 20), stage 1A, grade 2 EC; and G6 (n = 20), stage 1A, grade 3 EC. TRPM2 and TRPM7 genes were analyzed with qRT-PCR inparaffin-embedded tissue samples. Under light microscopy, TRPM2 and TRPM7 immunostaining scores of the samples taken frompolylysine slides were evaluated.Results: Compared to G1, TRPM2 mRNA gene expression was significantly downregulated in G3 and G5. TRPM2 immunoreactivityscores were similar in all groups. TRPM7 mRNA gene expression was significantly downregulated in G2, G3, and G6 when compared toG1. TRPM7 immunoreactivity scores were similar in G1, G2, and G3, but significantly decreased in G4, G5, and G6.Conclusion: Reduction in TRPM7 ion channel activity may be a progression marker for endometrial hyperplasia regardless of theatypical criteria.

___

  • 1. Ellenson LH, Ronnett BM, Kurman RJ. Precursor lesions of endometrial carcinoma. In: Kurman RJ, Ellenson LH, Ronnett BM, editors. Blaustein’s Pathology of the Female Genital Tract. 8th ed. Boston, MA, USA: Springer; 2011. pp. 359-392.
  • 2. Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. Lancet 2005; 366: 491-505.
  • 3. Armstrong AJ, Hurd WW, Elguero S, Barker NM, Zanotti KM. Diagnosis and management of endometrial hyperplasia. J Minim Invasive Gynecol 2012; 19: 562-571.
  • 4. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long term study of ‘untreated’ hyperplasia in 170 patients. Cancer 1985; 56: 403-412.
  • 5. Tabata T, Yamawaki T, Yabana T, Ida M, Nishimura K, Nose Y. Natural history of endometrial hyperplasia: study of 77 patients. Arch Gynecol Obstet 2001; 265: 85-88.
  • 6. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87-108.
  • 7. Sherman ME. Theories of endometrial carcinogenesis: a multidisciplinary approach. Mod Pathol 2000; 13: 295-308.
  • 8. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2016; 66: 7-30.
  • 9. Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, Heintz AP, Ngan HY, Pecorelli S. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006; 1: 105-143.
  • 10. Gautier M, Dhennin-Duthille I, Ay AS, Rybarczyk P, Korichneva I, Ouadid- Ahidouch H. New insights into pharmacological tools to TR (i)P cancer up. Br J Pharmacol 2014; 171: 2582-2592.
  • 11. Guinamard R, Sallé L, Simard C. The non-selective monovalent cationic channels TRPM4 and TRPM5. Adv Exp Med Biol 2011; 704: 147-171.
  • 12. Wu LJ, Sweet TB, Clapham DE. Current progress in the mammalian TRP ion channel family. International Union of Basic and Clinical Pharmacology. LXXVI. Pharmacol Rev 2010; 62: 381-404.
  • 13. Sharma M, Mishra B, Vandana, Saikia UN, Bahl A, Ratho RK, Talwar KK. Ribonucleic acid extraction from archival formalin fixed paraffin embedded myocardial tissues for gene expression and pathogen detection. J Clin Lab Anal 2012; 26: 279-285.
  • 14. Inoue K, Xiong ZG. Silencing TRPM7 promotes growth/ proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway. Cardiovasc Res 2009; 83: 547-57.
  • 15. Yao X, Garland CJ. Recent developments in vascular endothelial cell transient receptor potential channels. Circ Res 2005; 97: 853-863.
  • 16. Wang J, Liao QJ, Zhang Y, Zhou H, Luo CH, Tang J, Wang Y, Tang Y, Zhao M, Zhao XH et al. TRPM7 is required for ovarian cancer cell growth, migration and invasion. Biochem Biophys Res Commun 2014; 454: 547-553.
  • 17. Carter JH, Douglass LE, Deddens JA, Colligan BM, Bhatt TR, Pemberton JO, Konicek S, Hom J, Marshall M, Graff JR. Pak-1 expression increases with progression of colorectal carcinomas to metastasis. Clin Cancer Res 2004; 10: 3448-3456.
  • 18. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001; 69: 89-95.
  • 19. Sanderson PA, Critchley HO, Williams AR, Arends MJ, Saunders PT. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum Reprod Update 2017; 23: 232- 254.
  • 20. Upson K, Allison KH, Reed SD, Jordan CD, Newton KM, Swisher EM, Doherty JA, Garcia RL. Biomarkers of progestin therapy resistance and endometrial hyperplasia progression. Am J Obstet Gynecol 2012; 207: 36.e1-36.e8.
  • 21. Erkanli S, Bolat F, Kayaselcuk F, Demirhan B, Kuscu E. COX2 and survivin are overexpressed and positively correlated in endometrial carcinoma. Gynecol Oncol 2007; 104: 320-325.
  • 22. Horrée N, van Diest PJ, Sie-Go DMDS, Heintz APM. The invasive front in endometrial carcinoma: higher proliferation and associated derailment of cell cycle regulators. Hum Pathol 2007; 38: 1232-1238.
  • 23. Kurdoglu M, Kucukaydin Z, Kurdoglu Z, Bulut G, Unlu Y, Ozen S. Expression of laminin receptor 1 in normal, hyperplastic, and malignant endometrium. Int J Gynecol Pathol 2018 (in press).
  • 24. Voets T, Talavera K, Owsianik G, Nilius B. Sensing with TRP channels. Nat Chem Biol 2005; 1: 85-92.
  • 25. Dorr J, Fecher-Trost C. TRP channels in female reproductive organs and placenta. Adv Exp Med Biol 2011; 704: 909-928.
  • 26. Yang H, Choi KC, Hyun SH, Jeung EB. Coexpression and estrogen-mediated regulation of TRPV6 and PMCA1 in the human endometrium during the menstrual cycle. Mol Reprod Dev 2011; 78: 274-282.
  • 27. Kawarabayashi Y, Hai L, Honda A, Horiuchi S, Tsujioka H, Ichikawa J, Inoue R. Critical role of TRPC1-mediated Ca2+ entry in decidualization of human endometrial stromal cells. Mol Endocrinol 2012; 26: 846-858.
  • 28. Park YR, Chun JN, So I. Data-driven analysis of TRP channels in cancer: linking variation in gene expression to clinical significance. Cancer Genomics Proteomics 2016; 13: 83-90.
  • 29. Hiroi H, Momoeda M, Watanabe T, Ito M, Ikeda K, Tsutsumi R, Hosokawa Y, Koizumi M, Zenri F, Muramatsu M et al. Expression and regulation of transient receptor potential cation channel, subfamily M, member 2 (TRPM2) in human endometrium. Mol Cell Endocrinol 2013; 365: 146-152.
  • 30. Kordek R, Potemski P, Kusinska R, Pluciennik E, Bednarek A. Basal keratin expression in breast cancer by quantification of mRNA and by immunohistochemistry. J Exp Clin Cancer Res 2010; 29: 39.
  • 31. Paja FM, Ugalde OA, Fuertes TE, Oleaga AA. Immunohistochemical detection of the BRAF V600E mutation in papillary thyroid carcinoma. Evaluation against real-time polymerase chain reaction. Endocrinol Diabetes Nutr 2017; 64: 75-81.
  • 32. Ahn C, Yang H, Hong EJ, Jeung EB. Regulation and localization of transient receptor potential melastatin 2 in rat uterus. Reprod Sci 2014; 21: 1288-1295.
  • 33. Yee NS, Kazi AA, Yee RK. Cellular and developmental biology of TRPM7 channel-kinase: Implicated roles in cancer. Cells 2014; 3: 751-777.
  • 34. Fleig A, Chubanov V. TRPM7 mammalian transient receptor potential (TRP) cation channels. In: Nilius B, Flockerzi V, editors. Handbook of Experimental Pharmacology 222. Berlin, Germany: Springer-Verlag; 2014. pp. 521-522.
  • 35. Cabezas-Bratesco D, Brauchi S, Gonzales-Teuber V, Steinberg X, Valencia I, Colenso C. The different roles of the channelkinases TRPM6 and TRPM7. Curr Med Chem 2015; 22: 2943- 2953.
  • 36. Gautier M, Perrière M, Monet M, Vanlaeys A, Korichneva I, Dhennin-Duthille I, Ouadid-Ahidouch H. Recent advances in oncogenic roles of the TRPM7 chanzyme. Curr Med Chem 2016; 23: 4092-4107.
  • 37. Nakashima S, Shiozaki A, Ichikawa D, Hikami S, Kosuga T, Konishi H, Komatsu S, Fujiwara H, Okamoto K, Kishimoto M et al. Transient receptor potential melastatin 7 as an independent prognostic factor in human esophageal squamous cell carcinoma. Anticancer Res 2017; 37: 1161-1167.
  • 38. Rybarczyk P, Gautier M, Hague F, Dhennin-Duthille I, Chatelain D, Kerr-Conte J, Pattou F, Regimbeau JM, Sevestre H, Ouadid-Ahidouch H. Transient receptor potential melastatinrelated 7 channel is overexpressed in human pancreatic ductal adenocarcinomas and regulates human pancreatic cancer cell migration. Int J Cancer 2012; 131: 851-861.
  • 39. De Clercq K, Held K, Van Bree R, Meuleman C, Peeraer K, Tomassetti C, Voets T, D’Hooghe T, Vriens J. Functional expression of transient receptor potential channels in human endometrial stromal cells during the luteal phase of the menstrual cycle. Hum Reprod 2015; 30: 1421-1436.
  • 40. Ng NM, Jiang SP, Lv ZQ. Retrovirus-mediated siRNA targeting TRPM7 gene induces apoptosis in RBL-2H3 cells. Eur Rev Med Pharmacol Sci 2012; 16: 1172-1178.
  • 41. DH, Grant CE, Hill CE. Differential expression of TRPM7 in rat hepatoma and embryonic and adult hepatocytes. Can J Physiol Pharmacol 2012; 90: 435-444.
  • 42. Sahni J, Scharenberg AM. TRPM7 ion channels are required for sustained phosphoinositide 3-kinase signaling in lymphocytes. Cell Metab 2008; 8: 84-93.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Nesrin ÇAKICI, Alper AKÇALI, Nükhet Nilüfer ZORBA

Nima Montazeri NAJAFABADY, Mohammad Hossein DABBAGHMANESH, Rajeeh MOHAMADIAN-AMIRI, Marzieh BAKHSHAYESHKARAM, Gholamhossein Ranjbar OMRANI

Prevalence of atopy and allergic rhinitis in patients with adult non-cystic fibrosis bronchiectasis

Mehmet Atilla UYSAL, Rana IŞIK, Derya ÜNAL, Güngör ÇAMSARI, Elif Yelda NİKSARLIOĞLU

The results of nasopharyngeal cancer patients treated by simultaneous integrated boost technique and concomitant chemotherapy

Şeyda TÜRKÖLMEZ, Dinçer YEĞEN, İclal ÇETİNDAĞ, Atiye Yılmaz ÖZSAVRAN, Karabekir ERCAN, Mehmet Faik CETİNDAĞ, Bülent YALÇIN

Mortality predictors of patients suffering of acute pancreatitis and development of intraabdominal hypertension

Predrag STEVANOVIC, Maja STOJANOVIC, Petar SVORCAN, Aleksandar KARAMARKOVIC, Nebojsa LADJEVIC, Radmilo JANKOVIC

Azam AMIRIAN, Zahra ZAFARI, Zohre SHARIFI, Alireza KORDAFSHARI, Morteza KARIMIPOOR, Sirous ZEINALI

Characterization and haplotype study of 6 novel STR markers related to the KCNQ1 gene in heterogeneous cardiovascular disorders in the Iranian population

Zahra ZAFARI, Morteza KARIMIPOOR, Sirous ZEINALI, Azam AMIRIAN, Alireza KORDAFSHARI, Zohreh SHARIFI

The impact of JAK/STAT inhibitor ruxolitinib on the genesis of lymphoproliferative diseases

İbrahim Celalettin HAZNEDAROĞLU, Salih AKSU, Nilgün SAYINALP, Seyhan TÜRK, Osama JAVAD, Can TÜRK, Elif Sena TEMİRCİ, Müfide OKAY

Investigation of the relationship between ischemic stroke and endothelial nitric oxide synthase gene polymorphisms [G894T, intron 4 VNTR and T786C]

Serhat TOKGÖZ, Mahmut Selman YILDIRIM, Mehmet Sinan İYİSOY, Süleyman Ömer ANLIAÇIK, Ayşe GÜL ZAMANİ

Is there any difference between endometrial hyperplasia and endometrial carcinoma in terms of expression of TRPM2 and TRPM7 ion channels?

Gökhan ARTAŞ, Şehmus PALA, İlay BURAN, Emre YALÇIN, Ebru ÖNALAN, Remzi ATILGAN, Tuncay KULOĞLU