Role of Microsatellites Instability in Carcinogenesis of Postcricoid Carcinoma on Top of Plummer-Vinson Syndrome

Abstract

To develop a molecular pattern that might help in understanding carcinogenesis of postcricoid carcinoma (PCC) on top of Plummer-Vinson syndrome (PVS) in a prospective controlled study. Twenty-four patients with PVS were diagnosed and followed up over a 4 year period, during which eight of them showed malignant change to PCC. Twenty volunteers free of neoplastic diseases were included as a control group. In the two groups, DNA extraction from mononuclear peripheral blood cells, and analysis of loss of heterozygosity (LOH) and microsatellite instability (MSI) using six paired simple tandem repeats (STRs) primers were done. The molecular weight of each STRs locus was scored and statistical correlations were performed. LOH occurred in 55.6 and 72.9% of PVS and PCC cases compared to 25% of control group. At loci D17S695, D9S753 and D9S171, LOH occurred in 54.2, 66.7, and 70.8% of PVS cases; and in 62.5% of PCC cases for each locus compared to 15, 25 and 45% of control cases. D3S1286 and CFS1-R displayed the highest frequency of LOH in PCC (100% for each) while recorded in 58.3 and 33.3% in PVS compared to 30 and 0% in control cases. Certain genetic events tend to occur as early and late events in malignant change of PVS to PCC. Detection of these events may help in understanding carcinogenesis and in early detection of malignancy. CFS1-R is the most informative marker of tumor progression.

Plummer-Vinson Syndrome and Esophageal Cancer in an Endoscopy Center of Dakar

“…In southern countries where economic resources are limited, cases of PVS are still described [1]- [7].…”

“…In Africa and Asia, cases of PVS are reported in some regions due to poor sociodemographic conditions [1]- [7].…”

“…Its association with middle esophagus or distal esophagus cancer is exceptional [7] [12] [13]. Malignant degeneration occurs in 3% to 15% of cases [9] [10].…”

Long-term evolution of squamous-cell cancer in Plummer-Vinson syndrome

“…In a study by Chisholm, covering a total of 240 PVS patients, 72 being the author’s own series, the long-term follow-up results of these patients revealed that 23 patients developed malignities of the upper digestive system and only 5 (2%) of these patients had oesophageal cancer [ 11 ]. Since not all patients have malignity development, and despite genetic analysis studies for the prediction of cancer development not being covered by routine practices, there are studies on the subject as well [ 12 , 13 ]. Badawy et al suggested in their study that cytogenetic analysis should be performed for PVS patients as a polymorphic marker called CFS1-R, which was detected on the fifth chromosome, was seen in all the cases with post-cricoid cancer [ 12 ].…”

“…Since not all patients have malignity development, and despite genetic analysis studies for the prediction of cancer development not being covered by routine practices, there are studies on the subject as well [ 12 , 13 ]. Badawy et al suggested in their study that cytogenetic analysis should be performed for PVS patients as a polymorphic marker called CFS1-R, which was detected on the fifth chromosome, was seen in all the cases with post-cricoid cancer [ 12 ].…”