Advertisement

Annals of Surgical Oncology

, Volume 22, Issue 11, pp 3659–3665 | Cite as

Molecular Characteristics of Basaloid Squamous Cell Carcinoma of the Esophagus: Analysis of KRAS, BRAF, and PIK3CA Mutations and LINE-1 Methylation

  • Yoshifumi Baba
  • Takatsugu Ishimoto
  • Kazuto Harada
  • Keisuke Kosumi
  • Asuka Murata
  • Keisuke Miyake
  • Yukiharu Hiyoshi
  • Junji Kurashige
  • Masaaki Iwatsuki
  • Shiro Iwagami
  • Yuji Miyamoto
  • Yasuo Sakamoto
  • Naoya Yoshida
  • Eiji Oki
  • Ken-ichi Iyama
  • Masayuki Watanabe
  • Hideo BabaEmail author
Gastrointestinal Oncology

Abstract

Background

Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics, and was recently recognized as a variant of squamous cell carcinoma (SCC). We previously revealed genetic and epigenetic alterations associated with esophageal SCCs in relation to clinical outcome, including mutations in KRAS, BRAF, and PIK3CA, p53 expression, and long interspersed nucleotide element-1 (LINE-1) methylation, a surrogate marker for global DNA methylation level. In this study, we explored these features in BSCC.

Methods

A database of 502 esophageal cancers was used to evaluate the clinical and molecular characteristics of BSCC. KRAS, BRAF, and PIK3CA mutations and LINE-1 methylation were analyzed by pyrosequencing.

Results

Of 502 tumors, 22 (4.4 %) were pathologically diagnosed as BSCC, and 440 (87 %) as SCC. No prognostic differences between BSCC and SCC cases were identified (p = 0.41). KRAS or BRAF mutations were not observed in BSCCs. While 23 % of SCC tumors harbored a PIK3CA mutation, all BSCC cases were wild-type for PIK3CA (p = 0.002), and there were no differences in p53 expression between BSCCs and SCCs (p = 0.57), as assessed by immunohistochemistry. Furthermore, BSCC tissues exhibited significantly lower levels of LINE-1 methylation than SCC tissues (p < 0.0001).

Conclusions

These findings imply that esophageal BSCC and SCC retain different cellular phenotypes with distinct genetic and epigenetic alterations; thus, tailored therapeutic strategies should be developed against each cancer type.

Keywords

Squamous Cell Carcinoma Esophageal Cancer Esophageal Squamous Cell Carcinoma PIK3CA Mutation Squamous Cell Carcinoma Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Disclosure

Yoshifumi Baba, Takatsugu Ishimoto, Kazuto Harada, Keisuke Kosumi, Asuka Murata, Keisuke Miyake, Yukiharu Hiyoshi, Junji Kurashige, Masaaki Iwatsuki, Shiro Iwagami, Yuji Miyamoto, Yasuo Sakamoto, Naoya Yoshida, Eiji Oki, Ken-ichi Iyama, Masayuki Watanabe, and Hideo Baba have no conflicts of interest or competing interests to report.

Supplementary material

10434_2015_4445_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 kb)

References

  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.CrossRefPubMedGoogle Scholar
  2. 2.
    Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–52.CrossRefPubMedGoogle Scholar
  3. 3.
    Wain SL, Kier R, Vollmer RT, et al. Basaloid-squamous carcinoma of the tongue, hypopharynx, and larynx: report of 10 cases. Hum Pathol. 1986;17:1158–66.CrossRefPubMedGoogle Scholar
  4. 4.
    Sarbia M, Verreet P, Bittinger F, et al. Basaloid squamous cell carcinoma of the esophagus: diagnosis and prognosis. Cancer. 1997;79:1871–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Morice WG, Ferreiro JA. Distinction of basaloid squamous cell carcinoma from adenoid cystic and small cell undifferentiated carcinoma by immunohistochemistry. Hum Pathol. 1998;29:609–12.CrossRefPubMedGoogle Scholar
  6. 6.
    Cho KJ, Jang JJ, Lee SS, et al. Basaloid squamous carcinoma of the oesophagus: a distinct neoplasm with multipotential differentiation. Histopathology. 2000;36:331–40.CrossRefPubMedGoogle Scholar
  7. 7.
    Li TJ, Zhang YX, Wen J, et al. Basaloid squamous cell carcinoma of the esophagus with or without adenoid cystic features. Arch Pathol Lab Med. 2004;128:1124–30.PubMedGoogle Scholar
  8. 8.
    Chen SB, Weng HR, Wang G, et al. Basaloid squamous cell carcinoma of the esophagus. J Cancer Res Clin Oncol. 2012;138:1165–71.CrossRefPubMedGoogle Scholar
  9. 9.
    Lam KY, Law S, Luk JM, et al. Oesophageal basaloid squamous cell carcinoma: a unique clinicopathological entity with telomerase activity as a prognostic indicator. J Pathol. 2001;195:435–42.CrossRefPubMedGoogle Scholar
  10. 10.
    Imamhasan A, Mitomi H, Saito T, et al. Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas. Hum Pathol. 2012;43:2012–23.CrossRefPubMedGoogle Scholar
  11. 11.
    Ohashi K, Horiguchi S, Moriyama S, et al. Superficial basaloid squamous carcinoma of the esophagus. A clinicopathological and immunohistochemical study of 12 cases. Pathol Res Pract. 2003;199:713–21.PubMedGoogle Scholar
  12. 12.
    Abe K, Sasano H, Itakura Y, et al. Basaloid-squamous carcinoma of the esophagus. A clinicopathologic, DNA ploidy, and immunohistochemical study of seven cases. Am J Surg Pathol. 1996;20:453–61.CrossRefPubMedGoogle Scholar
  13. 13.
    Koide N, Koike S, Adachi W, et al. Immunohistochemical expression of bcl-2 protein in squamous cell carcinoma and basaloid carcinoma of the esophagus. Surg Today. 1997;27:685–91.CrossRefPubMedGoogle Scholar
  14. 14.
    Sarbia M, Loberg C, Wolter M, et al. Expression of Bcl-2 and amplification of c-myc are frequent in basaloid squamous cell carcinomas of the esophagus. Am J Pathol. 1999;155:1027–32.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Owonikoko T, Loberg C, Gabbert HE, et al. Comparative analysis of basaloid and typical squamous cell carcinoma of the oesophagus: a molecular biological and immunohistochemical study. J Pathol. 2001;193:155–61.CrossRefPubMedGoogle Scholar
  16. 16.
    Bellizzi AM, Woodford RL, Moskaluk CA, et al. Basaloid squamous cell carcinoma of the esophagus: assessment for high-risk human papillomavirus and related molecular markers. Am J Surg Pathol. 2009;33:1608–14.CrossRefPubMedGoogle Scholar
  17. 17.
    Shigaki H, Baba Y, Watanabe M, et al. KRAS and BRAF mutations in 203 esophageal squamous cell carcinomas: pyrosequencing technology and literature review. Ann Surg Oncol 2013;20 Suppl 3:S485–91.CrossRefPubMedGoogle Scholar
  18. 18.
    Shigaki H, Baba Y, Watanabe M, et al. PIK3CA mutation is associated with a favorable prognosis among patients with curatively resected esophageal squamous cell carcinoma. Clin Cancer Res. 2013;19:2451–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Murata A, Baba Y, Watanabe M, et al. p53 immunohistochemical expression and patient prognosis in esophageal squamous cell carcinoma. Med Oncol. 2013;30:728.CrossRefPubMedGoogle Scholar
  20. 20.
    Iwagami S, Baba Y, Watanabe M, et al. LINE-1 hypomethylation is associated with a poor prognosis among patients with curatively resected esophageal squamous cell carcinoma. Ann Surg. 2013;257:449–55.CrossRefPubMedGoogle Scholar
  21. 21.
    Baba Y, Watanabe M, Shigaki H, et al. Negative lymph-node count is associated with survival in patients with resected esophageal squamous cell carcinoma. Surgery. 2013;153:234–41.CrossRefPubMedGoogle Scholar
  22. 22.
    Ogino S, Kawasaki T, Nosho K, et al. LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer. Int J Cancer. 2008;122:2767–73.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Ogino S, Nosho K, Kirkner GJ, et al. A cohort study of tumoral LINE-1 hypomethylation and prognosis in colon cancer. J Natl Cancer Inst. 2008;100:1734–8.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Baba Y, Huttenhower C, Nosho K, et al. Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors. Mol Cancer. 2010;9:125.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Martini M, Vecchione L, Siena S, et al. Targeted therapies: how personal should we go? Nat Rev Clin Oncol. 2012;9:87–97.CrossRefGoogle Scholar
  26. 26.
    McNamara MJ, Adelstein DJ. Current developments in the management of locally advanced esophageal cancer. Curr Oncol Rep. 2012;14:342–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Walther A, Johnstone E, Swanton C, et al. Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer. 2009;9:489–99.CrossRefPubMedGoogle Scholar
  28. 28.
    Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7:606–19.CrossRefPubMedGoogle Scholar
  29. 29.
    Taby R, Issa JP. Cancer epigenetics. CA Cancer J Clin. 2010;60:376–92.CrossRefPubMedGoogle Scholar
  30. 30.
    Gaudet F, Hodgson JG, Eden A, et al. Induction of tumors in mice by genomic hypomethylation. Science. 2003;300:489–92.CrossRefPubMedGoogle Scholar
  31. 31.
    Cordaux R, Batzer MA. The impact of retrotransposons on human genome evolution. Nat Rev Genet. 2009;10:691–703.PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Baba Y, Watanabe M, Murata A, et al. LINE-1 hypomethylation, DNA copy number alterations, and CDK6 amplification in esophageal squamous cell carcinoma. Clin Cancer Res. 2014;20:1114–24.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Yoshifumi Baba
    • 1
  • Takatsugu Ishimoto
    • 1
  • Kazuto Harada
    • 1
  • Keisuke Kosumi
    • 1
  • Asuka Murata
    • 1
  • Keisuke Miyake
    • 1
  • Yukiharu Hiyoshi
    • 1
  • Junji Kurashige
    • 1
  • Masaaki Iwatsuki
    • 1
  • Shiro Iwagami
    • 1
  • Yuji Miyamoto
    • 1
  • Yasuo Sakamoto
    • 1
  • Naoya Yoshida
    • 1
  • Eiji Oki
    • 2
  • Ken-ichi Iyama
    • 3
  • Masayuki Watanabe
    • 4
  • Hideo Baba
    • 1
    Email author
  1. 1.Department of Gastroenterological Surgery, Graduate School of Medical ScienceKumamoto UniversityKumamoto CityJapan
  2. 2.Department of Surgery and Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of PathologyKumamoto General HospitalKumamotoJapan
  4. 4.Department of Gastroenterological Surgery, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan

Personalised recommendations