Skip to main content
SpringerLink
Log in

RRM1, ERCC1 and TS1 Immunofluorescence Expression in Leiomyosarcoma: A Tissue Microarray Study with Clinical Outcome Correlation Analysis

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

ERCC1, RRM1 and TS1 are reportedly linked to chemotherapy resistance in lung and other cancers. However, there are currently no studies reporting the relationship between these genes and clinical parameters in leiomyosarcomas.

Method: This study investigated the expression pattern of ERCC1, RRM1 and TS1 in forty-four leiomyosarcoma samples by the use of tissue microarray (TMA), immunofluorescence and AQUA methods. The results were then analyzed for expression level and correlations were made with clinical outcome to determine their potential prognostic value in leiomyosarcoma.

Results: In the forty-four samples studied, the expression level of these three proteins can be well quantified in the AQUA system and reflected by the AQUA score. RRM1 and ERCC1 expression levels did not show any relationship with overall survival. However, a correlation was found between TS1 expression in the cytoplasm and overall survival. The high expression group had a shorter overall survival time (log-rank p = 0.0498). This trend was confirmed by the Cox proportional hazards model.

Discussion: The poor overall survival of leiomyosarcoma is linked to TS1 cytoplasm expression which may be useful in predicting prognoses of this tumor, methods targeting expression of TS1 may lead to improved overall survival in leiomyosarcoma, though more detailed information regarding treatment information and a larger sample size is needed to confirm this phenomenon.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Damiano G, Di Ganci S, Palumbo VD, Spinelli G, De Luca S, Cudia B, Tomasello G, Lo Monte AI (2012) Gastric leiomyosarcoma case report and review of literature. Clin Ter 163(4):e181–e184

    CAS  PubMed  Google Scholar 

  2. Yamamoto H, Handa M, Tobo T, Setsu N, Fujita K, Oshiro Y, Mihara Y, Yoshikawa Y, Oda Y (2013) Clinicopathological features of primary leiomyosarcoma of the gastrointestinal tract following recognition of gastrointestinal stromal tumors. Histopathology 63:194–207

    Article  PubMed  Google Scholar 

  3. Hadoux J, Morice P, Lhommé C, Duvillard P, Balleyguier C, Haie-Meder C, Gouy S, Uzan C, Mazeron R, Tazi Y, Leary A, Duffaud F, Pautier P (2013) Uterine leiomyosarcoma: epidemiology, pathology, biology, diagnosis, prognosis and treatment. Bull Cancer. Sep. 100(9):903–915. doi:10.1684/bdc.2013.1801

    Google Scholar 

  4. Xu J, Zhang T, Wang T, You L, Zhao Y (2013) Clinical characteristics and prognosis of primary leiomyosarcoma of the pancreas: a systematic review. World J Surg Oncol. 11:290. doi:10.1186/1477-7819-11-290

    Article  PubMed  PubMed Central  Google Scholar 

  5. Nappi L, Mele G, Angioni S, Cicinelli E, Greco P (2014) Uterine leiomyosarcoma: report of three cases and review of the literature. Eur J Gynaecol Oncol 35:328–331

    CAS  PubMed  Google Scholar 

  6. Agaimy A, Weunsch PH (2007) True smooth muscle neoplasms of the gastrointestinal tract: morphological spectrum and classification in a series of 85 cases from a single institute. Langenbecks Arch Surg 392:75–81

    Article  PubMed  Google Scholar 

  7. Itoga M, Ito W, Ueki S, Takeda M, Moritoki Y, Kobayashi Y, Chihara M, Suzuki N (2013) Sasaki H (2013) Chihara J. Lung metastasis from perineal leiomyosarcoma: a case report and a review of the Japanese literature. Case Rep Med. 496:304. doi:10.1155/2013/496,304

    Google Scholar 

  8. Barwad A, Khandelwal N, Vyas S, Gogoi D, Dey P (2011) Primary leiomyosarcoma of the prostate with lung metastasis: report of a case diagnosed by fine-needle aspiration cytology. Diagn Cytopathol. 39:700–702. doi:10.1002/dc.21539

    Article  PubMed  Google Scholar 

  9. Alonso Gómez J, Arjona Sánchez Á, Martínez Cecilia D, Díaz Nieto R, Roldán de la Rúa J, Valverde Martínez A, Lizárraga Febres E, Padillo Ruiz J, Rufián Peña S (2012) Uterine leiomyosarcoma metastasis to the pancreas: report of a case and review of the literature. J Gastrointest Cancer 43:361–363. doi:10.1007/s12029-010-9172-x

    Article  PubMed  Google Scholar 

  10. Luis J, Ejtehadi F, Howlett DC, Donnellan IM (2015) Leiomyosarcoma of the small bowel: Report of a case and review of the literature. Int J Surg Case Rep 6C:51–54. doi:10.1016/j.ijscr.2014.11.009

    Article  PubMed  Google Scholar 

  11. Lazar A, Evans HL, Shipley J (2013) Leiomyosarcoma. In: WHO Classification of Tumours of Soft Tissue and Bone. IARC, France, pp. 111–113

    Google Scholar 

  12. Fernandez-Flores A. (2010) Cutaneous leiomyomas and leiomyosarcomas an immunohistochemical study with p53.Rom J Morphol Embryol 51:295–298.

  13. Abdulkader I, Cameselle-Teijeiro J, Gude F, Fraga M, Varela-Durán J, Barreiro F, Forteza J (2002) Predictors of malignant behaviour in gastrointestinal stromal tumours: a clinicopathological study of 34 cases. Eur J Surg 168:288–296

    Article  PubMed  Google Scholar 

  14. Bergman AM, Pinedo HM, Jongsma APM, et al. (1999) Decreased resistance to gemcitabine (2_2_-difluorodeoxycytidine) of cytosine arabinoside-resistant myeloblastic murine and rat leukemia cell lines: role of altered activity and substrate specificity of deoxycytidine kinase. Biochem Pharmacol 57:397–406

    Article  CAS  PubMed  Google Scholar 

  15. Bepler G, Sharma S, Cantor A, et al. (2004) RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer. J Clin Oncol 22:1878–1886

    Article  CAS  PubMed  Google Scholar 

  16. Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, Sharma A, Simon G (2006) RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol 24:4731–4737

    Article  CAS  PubMed  Google Scholar 

  17. Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G (2007) DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med 356:800–808

    Article  CAS  PubMed  Google Scholar 

  18. Simon G, Sharma A, Li X, Hazelton T, Walsh F, Williams C, Chiappori A, Haura E, Tanvetyanon T, Antonia S, Cantor A, Bepler G (2007). Feasibility and efficacy of molecular analysis-directed individualized therapy in advanced non-small-cell lung cancer. J Clin Oncol. Jul 1;25(19):2741–6.

  19. Simon GR, Sharma S, Cantor A, Smith P, Bepler G (2005) ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer. Chest 127:978–983

    Article  PubMed  Google Scholar 

  20. Zheng Z, Li X, Schell MJ, Chen T, Boulware D, Robinson L, Sommers E, Bepler G (2008) Thymidylate synthase in situ protein expression and survival in stage I nonsmall-cell lung cancer. Cancer 112:2765–2773

    Article  CAS  PubMed  Google Scholar 

  21. Chu E, Callender MA, Farrell MP, Schmitz JC (2003) Thymidylate synthase inhibitors as anticancer reagent TS1: from bench to bedside. Cancer Chemother Pharmacol. 52(Suppl 1):S80–S89

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Sam D. Zheng & Katherine Bui

  2. Department of Pathology, Thoracic Oncology, H. Lee Moffitt Cancer Center, MCC 2nd FL, 12029 Magnolia Drive, Tampa, FL, 33647, USA

    Alberto Chiappori & Marilyn M. Bui

  3. Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    Gerold Bepler

Authors
  1. Sam D. Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katherine Bui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alberto Chiappori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gerold Bepler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marilyn M. Bui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marilyn M. Bui.

Additional information

Gerold Bepler and Marilyn M. Bui equally contributed to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, S.D., Bui, K., Chiappori, A. et al. RRM1, ERCC1 and TS1 Immunofluorescence Expression in Leiomyosarcoma: A Tissue Microarray Study with Clinical Outcome Correlation Analysis. Pathol. Oncol. Res. 22, 477–482 (2016). https://doi.org/10.1007/s12253-015-0021-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-015-0021-x

Keywords

Search

Navigation