LOH detected by microsatellite markers reveals the clonal origin of recurrent laryngeal squamous cell carcinoma

Abstract

Background: The question of whether "recurrent" laryngeal carcinoma is truly a new tumour with a clonal origin that differs from that of the primary tumour has remained unanswered. The objective of this study was to determine whether recurrent tumours have the same genetic basis as primary tumours, as the answer to this question is important for the development of treatment strategies.

Materials and methods: Matched samples consisting of primary tumour, recurrent tumour and normal tissue were obtained from the same patient. A total of 37 patients with laryngeal cancer were examined for loss of heterozygosity (LOH) on the 3p, 5p, 7q, 8p, 9p, 13p, 17p and 18q chromosomal arms using PCR to amplify microsatellite markers. All patients were routinely followed up and 5-year survival rates were calculated using directly calculating method and Kaplan-Meier's method.

Results: A total of 28 out of 37 (75.6%) patients showed LOH at a minimum of one locus, and 19 out of 37 (51.3%) patients showed LOH at two loci. Primary and recurrent tumours in each patient showed identical allelic loss patterns and incidence rates. Patients without LOH had a longer average time to recurrence than patients with LOH (P<0.05). Additionally, patients with LOH had a longer average smoking duration prior to surgery than patients without LOH (P<0.05). The 5-year survival rates were 32.14%in patients with LOH versus 44.4% in patients without LOH.

Conclusions: The data indicate that primary and recurrent tumours have the same clonal origin. This result implies that we failed to radically resect the primary tumours and/or micrometastases in these patients. Consequently, some form of adjunctive therapy may be necessary. Additionally, the data indicate that the recurrence of laryngeal squamous cell carcinoma is closely related to chromosomal aberrations (specifically LOH).

Figure 1. An LOH-mode electrophoresis diagram.

A) A representative laryngeal LOH-mode electrophoresis diagram at D5S592. B) A representative laryngeal LOH-mode electrophoresis diagram at D9S171. TP, primary tumour; TR, recurrent tumour; N, normal tissue. The arrow indicates the missing band. The normal tissue was derived from areas adjacent to the tumour and served as a control.

Figure 2. Overall survival of patients without LOH and patients with LOH (P = 0.021).