Skip to main content

Advertisement

SpringerLink
Log in

Patterns of LC3A Autophagy Protein Expression in Keratoacanthomas

  • Original Paper
  • Published:
Head and Neck Pathology Aims and scope Submit manuscript

Abstract

To investigate the expression patterns of autophagy marker light chain protein 3 (LC3A) in keratoacanthoma (KA). KAs are generally regarded as benign but malignant behavior, including rare metastases, may occur. 85 KAs were assessed for the LC3A autophagic protein by immunohistochemistry. Diffuse cytoplasmic staining and a “stone-like structure” (SLS) characterized positive expression. Thirty-four out of 85 KAs (40%) had diffuse cytoplasmic LC3A immunostaining (percentage of positive cells ranging from 5 to 60%). In contrast, only 4 of the 85 KAs (4.7%) expressed SLSs. Only one SLS was detected per histologic section of each tumor. The p53 oncoprotein was encountered in all cases with expression ranging from 1 to 90% of cells (median 30%). The Ki-67 index was expressed in 63 cases (74% of cases; range 1–50% of cells; median value 5%). Neither of these two parameters nor diffuse cytoplasmic LC3A staining was significantly correlated with SLS expression or lack thereof. Expression of SLSs, a hallmark of malignancy, was found in 4.7% of KAs. Further study is necessary to determine whether this fraction represents the exceptional cases that harbor latent malignant potential.

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
Fig. 2

Similar content being viewed by others

References

  1. Savage JA, Maize JC, Sr. Keratoacanthoma clinical behavior: a systematic review. Am J Dermatopathol. 2014;36:422–9.

    PubMed  Google Scholar 

  2. Oellers P, Karp CL, Shah RR, et al. Conjunctival keratoacanthoma. Br J Ophthalmol. 2014;98:275–6.

    PubMed  Google Scholar 

  3. Ko CJ. Keratoacanthoma: facts and controversies. Clin Dermatol. 2010;28:254–61.

    PubMed  Google Scholar 

  4. Piscioli F, Boi S, Zumiani G, et al. A gigantic, metastasizing keratoacanthoma. Report of a case and discussion on classification. Am J Dermatopathol. 1984;6:123–9.

    CAS  PubMed  Google Scholar 

  5. Hodak E, Jones RE, Ackerman AB. Solitary keratoacanthoma is a squamous-cell carcinoma: three examples with metastases. Am J Dermatopathol. 1993;15:332–42.

    CAS  PubMed  Google Scholar 

  6. Mandrell JC, Santa Cruz D. Keratoacanthoma: hyperplasia, benign neoplasm, or a type of squamous cell carcinoma? Semin Diagn Pathol. 2009;26:150–63.

    PubMed  Google Scholar 

  7. Weedon D. Weedon’s skin pathology. Keratoacanthoma centrifugum marginatum. Edinburg: Churchill Livingstone Elsevier; 2010. p. 702–8.

    Google Scholar 

  8. Godbolt AM, Sullivan JJ, Weedon D. Keratoacanthoma with perineural invasion: a report of 40 cases. Australas J Dermatol. 2001;42:168–71.

    CAS  PubMed  Google Scholar 

  9. Weedon D, Malo J, Brooks D, et al. Keratoacanthoma: is it really a variant of squamous cell carcinoma? ANZ J Surg. 2010;80:129–30.

    PubMed  Google Scholar 

  10. Ra SH, Su A, Li X, et al. Keratoacanthoma and squamous cell carcinoma are distinct from a molecular perspective. Mod Pathol. 2015;28:799–806.

    CAS  PubMed  Google Scholar 

  11. Gleich T, Chiticariu E, Huber M, et al. Keratoacanthoma: a distinct entity? Exp Dermatol. 2016;25:85–91.

    PubMed  Google Scholar 

  12. Ogita A, Ansai SI, Misago N, et al. Histopathological diagnosis of epithelial crateriform tumors: Keratoacanthoma and other epithelial crateriform tumors. J Dermatol. 2016;43:1321–31.

    CAS  PubMed  Google Scholar 

  13. Manstein CH, Frauenhoffer CJ, Besden JE. Keratoacanthoma: is it a real entity? Ann Plast Surg. 1998;40:469–72.

    CAS  PubMed  Google Scholar 

  14. Sarma D. Keratoacanthoma should be reported as “well differentiated squamous cell carcinoma, Keratoacanthoma Type”: a dermatopathologist’s view. Internet J Dematol. 2006;5:1.

    Google Scholar 

  15. Goldenberg G, Patel S, Patel MJ, et al. Eruptive squamous cell carcinomas, keratoacanthoma type, arising in a multicolor tattoo. J Cutan Pathol. 2008;35:62–4.

    PubMed  Google Scholar 

  16. Sivridis E, Koukourakis MI, Zois CE, Ledaki I, Ferguson DJ, Harris AL, Gatter KC, Giatromanolaki A. LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas. Am J Pathol. 2010;176:2477–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Giatromanolaki A, Sivridis E, Mendrinos S, et al. Autophagy proteins in prostate cancer: relation with anaerobic metabolism and Gleason score. Urol Oncol. 2014;32:39.e11-8.

    PubMed  Google Scholar 

  18. Giatromanolaki A, Koukourakis MI, Harris AL, et al. Prognostic relevance of light chain 3 (LC3A) autophagy patterns in colorectal adenocarcinomas. J Clin Pathol. 2010;63:867–72.

    PubMed  Google Scholar 

  19. Sivridis E, Giatromanolaki A, Karpathiou G, et al. LC3A-positive “stone-like” structures in cutaneous squamous cell carcinomas. Am J Dermatopathol. 2011;33:285–90.

    PubMed  Google Scholar 

  20. Karpathiou G, Sivridis E, Koukourakis MI, et al. Light-chain 3A autophagic activity and prognostic significance in non-small cell lung carcinomas. Chest. 2011;140:127–34.

    PubMed  Google Scholar 

  21. Sivridis E, Koukourakis MI, Mendrinos SE, et al. Patterns of autophagy in urothelial cell carcinomas—the significance of “stone-like” structures (SLS) in transurethral resection biopsies. Urol Oncol. 2013;31:1254–60.

    PubMed  Google Scholar 

  22. Giatromanolaki A, Sivridis E, Mitrakas A, et al. Autophagy and lysosomal related protein expression patterns in human glioblastoma. Cancer Biol Ther. 2014;15:1468–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Sivridis E, Giatromanolaki A, Liberis V. Autophagy in endometrial carcinomas and prognostic relevance of ‘stone-like’ structures (SLS) What is destined for the atypical endometrial hyperplasia? Autophagy. 2011;7:74–82.

    CAS  PubMed  Google Scholar 

  24. Giatromanolaki A, Koukourakis M, Koutsopoulos, et al. Autophagy and hypoxia in colonic adenomas related to aggressive features. Colorectal Dis. 2013;15:e223-30.

    PubMed  Google Scholar 

  25. Liao W, Sun L, Wang C, Huang H, Liu J, Liao W, Shi M. LC3A-positive “stone-like” structures predict an adverse prognosis of gastric cancer. Anat Rec (Hoboken). 2014;297:653–62.

    CAS  Google Scholar 

  26. Xi SY, Lu JB, Chen JW, et al. The “stone-like” pattern of LC3A expression and its clinicopathologic significance in hepatocellular carcinoma. Biochem Biophys Res Commun. 2013;431:760–6.

    CAS  PubMed  Google Scholar 

  27. Spowart JE, Townsend KN, Huwait H, et al. The autophagy protein LC3A correlates with hypoxia and is a prognostic marker of patient survival in clear cell ovarian cancer. J Pathol. 2012;228:437–47.

    CAS  PubMed  Google Scholar 

  28. Sivridis E, Giatromanolaki A, Zois C, et al. The “stone-like” pattern of autophagy in human epithelial tumors and tumor-like lesions. An approach to the clinical outcome. Autophagy. 2010;6:122–5.

    Google Scholar 

  29. Feng Y, He D, Yao Z, Klionsky DJ. The machinery of macroautophagy. Cell Res. 2014;24:24–41.

    CAS  PubMed  Google Scholar 

  30. Mizushima N. Autophagy: process and function. Genes Dev. 2007;21:2861–73.

    CAS  PubMed  Google Scholar 

  31. Klionsky DJ, Baehrecke EH, Brumell JH, et al. A comprehensive glossary of autophagy-related molecules and processes (2nd ed.). Autophagy 2011;7:1273–94.

    PubMed  PubMed Central  Google Scholar 

  32. Musiwaro P, Smith M, Manifava M, et al. Characteristics and requirements of basal autophagy in HEK 293 cells. Autophagy. 2013;9:1407–17.

    CAS  PubMed  Google Scholar 

  33. Li LT, Jiang G, Chen Q, et al. Ki67 is a promising molecular target in the diagnosis of cancer (review). Mol Med Rep. 2015;11:1566–72.

    CAS  PubMed  Google Scholar 

  34. Joshi S, Schjølberg AR, Ekstrøm PO, et al. Tp53/p53 status in keratoacanthomas. J Cutan Pathol. 2016;43:571–8.

    PubMed  Google Scholar 

  35. Watanabe IC, Magalhães RF, de Moraes AM, et al. Keratoacanthoma and keratoacanthoma-like squamous cell carcinoma: similar morphology but different pathogenesis. Medicine (Baltimore). 2015;94:e934.

    Google Scholar 

  36. Martinet W, Roth L, De Meyer GRY, Standard immunohistochemical assays to assess autophagy in mammalian tissue. Cells. 2017;6(3):17.

    PubMed Central  Google Scholar 

  37. Brantsch KD, Meisner C, Schönfisch B, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol. 2008;9:713–20.

    PubMed  Google Scholar 

  38. Amorim E. Solitary fibrous tumor of the pleura: 3 case reports. Rev Assoc Med Bras. 2015;61:207–8.

    PubMed  Google Scholar 

  39. Thway K, Ng W, Noujaim J, et al. The current status of solitary fibrous tumor: diagnostic features, variants, and genetics. Int J Surg Pathol. 2016;24:281–92.

    CAS  PubMed  Google Scholar 

  40. Strickland KC, Nucci MR, Esselen KM, et al. Solitary fibrous tumor of the uterus presenting with lung metastases: a case report. Int J Gynecol Pathol. 2016;35:25–9.

    PubMed  Google Scholar 

  41. Akahane K, Kato K, Ogiso S, Sakaguchi K, et al. Malignant granular cell tumor of the breast: case report and literature review. Breast Cancer. 2015;22:317–23.

    PubMed  Google Scholar 

  42. Martignoni G, Pea M, Zampini C, et al. PEComas of the kidney and of the genitourinary tract. Semin Diagn Pathol. 2015;32:140–59.

    PubMed  Google Scholar 

  43. Doyle LA, Hornick JL, Fletcher CD. PEComa of the gastrointestinal tract: clinicopathologic study of 35 cases with evaluation of prognostic parameters. Am J Surg Pathol. 2013;37:1769–82.

    PubMed  Google Scholar 

  44. Do BA, Varshney R, Zawawi F, et al. Inflammatory myofibroblastic tumor of the larynx-a case report. J Voice. 2014;28:258–61.

    PubMed  Google Scholar 

  45. Lai LM, McCarville MB, Kirby P, et al. Shedding light on inflammatory pseudotumor in children: spotlight on inflammatory myofibroblastic tumor. Pediatr Radiol. 2015;45:1738–52.

    PubMed  Google Scholar 

  46. Strieth S, Hartschuh W, Pilz L, et al. Carcinoma-like vascular density in atypic keratoacanthoma suggests malignant progression. Br J Cancer. 2002;87:1301–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Chow TK, Chacko E, Cleary C, et al. Keratoacanthoma of the lower eyelid. Eye (Lond). 2005;19:689–90.

    CAS  Google Scholar 

  48. Clausen OP, Aass HC, Beigi M, et al. Are keratoacanthomas variants of squamous cell carcinomas? A comparison of chromosomal aberrations by comparative genomic hybridization. J Invest Dermatol. 2006;126:2308–15.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pathology, Democritus University of Thrace Medical School and University General Hospital of Alexandroupolis, 68100, Alexandroupolis, Greece

    Efthimios Sivridis, Ioannis M. Koukourakis, Stella Arelaki, Kostantina Balaska & Alexandra Giatromanolaki

  2. Departments of Dermatology, Democritus University of Thrace Medical School and University General Hospital of Alexandroupolis, 68100, Alexandroupolis, Greece

    Antonios Karpouzis

Authors
  1. Efthimios Sivridis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ioannis M. Koukourakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stella Arelaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kostantina Balaska
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonios Karpouzis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexandra Giatromanolaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Efthimios Sivridis.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sivridis, E., Koukourakis, I.M., Arelaki, S. et al. Patterns of LC3A Autophagy Protein Expression in Keratoacanthomas. Head and Neck Pathol 14, 150–155 (2020). https://doi.org/10.1007/s12105-019-01033-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-019-01033-1

Keywords

Search

Navigation