J Korean Med Sci.  2004 Jun;19(3):345-351. 10.3346/jkms.2004.19.3.345.

Loss of Heterozygosity on Chromosomes 3p,8p,9p and 17p in the Progression of Squamous Cell Carcinoma of the Larynx

Affiliations
  • 1Department of Otolaryngology-HNS, The Catholic University of Korea, College of Medicine, Seoul, Korea.
  • 2Department of Clinical Pathology, The Catholic University of Korea, College of Medicine, Seoul, Korea. lys9908@catholic.ac.kr
  • 3Department of Pathology, The Catholic University of Korea, College of Medicine, Seoul, Korea.

Abstract

Previous molecular genetic studies of laryngeal squamous cell carcinoma (SCC)have shown certain chromosomal regions with recurring alterations. But studies of sequential molecular alterations and genetic progression model of laryngeal SCC have not been clearly defined. To identify the chromosomal alterations associated with the carcinogenesis of laryngeal SCC, we analyzed genomic DNA from microdissected squamous metaplasia, squamous dysplasia, invasive SCC, and metastatic carcinoma samples from 22 laryngeal SCC patients for loss of heterozygosity (LOH) at microsatellite loci. Ten microsatellite markers on chromosome 3p, 8p, 9p, and 17p were used. LOH at 9p21 was observed in the all stages including squamous metaplasia, squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 17p13.1, 3p25 and 3p14.2 was observed from the squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 8p21.3-p22 was observed mainly from the invasive SCC and metastatic carcinoma. The results suggest that 9p21 in the early event, 17p13.1, 3p25 and 3p14.2 in the intermediate event and 8p21.3- p22 in the late event may be involved in the laryngeal carcinogenesis.

Keyword

Loss of Heterozygosity; Chromosomes; Laryngeal Neoplasms; Carcinoma, Squamous Cell

MeSH Terms

Carcinoma, Squamous Cell/*genetics/pathology
Chromosome Mapping
*Chromosomes, Human, Pair 17
*Chromosomes, Human, Pair 3
*Chromosomes, Human, Pair 8
*Chromosomes, Human, Pair 9
Disease Progression
Human
Laryngeal Neoplasms/*genetics
Larynx/pathology
*Loss of Heterozygosity
Lymphatic Metastasis
Metaplasia/pathology
Microsatellite Repeats
Neoplasm Metastasis

Figure

  • Fig. 1-1 Sections of laryngeal carcinoma (A) and metastatic lymph node (B) from case 4 showing the areas of metaplasia (M), dysplasia (D), invasive carcinoma (I), and lymph node metastatic carcinoma (L) (H&E, ×4).

  • Fig. 1-2 The magnified areas of metaplasia (M), dysplasia (D), invasive carcinoma (I), and lymph node metastatic carcinoma (L) before (A) and after (B) microdissection (H&E, ×100).

  • Fig. 2 Analysis of loss of heterozygosity according to the development and progression of laryngeal squamous cell carcinoma (case 2) showing allelic loss (arrow head) from metaplasia (IFNA, D9S171, D9S104) and from dysplasia (TP53, D3S1038, D3S1067), Four markers (D3S1234, D8S261, D8S258, D8S133) are homozygote (non-informative). N, normal; M, metaplasia; D, dysplasia; I, invasive carcinoma; L, lymph node metastasis.

  • Fig. 3 Analysis of loss of heterozygosity according to the development and progression of laryngeal squamous cell carcinoma (case 13) showing allelic loss (arrow head) from metaplasia (D9S171), from dysplasia (D3S1067, D3S1234, D8S133), and from invasive carcinoma (D8S261, D8S258). Four markers (IFNA, D9S104, TP53, D3S1038) are homozygote (non-informative). N, normal; M, metaplasia; D, dysplasia; I, invasive carcinoma; L, lymph node metastasis.


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