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Quantitative methylation analyses of resection margins predict local recurrences and disease-specific deaths in patients with head and neck squamous cell carcinomas.

Tan HK, Saulnier P, Auperin A, Lacroix L, Casiraghi O, Janot F, Fouret P, Temam S - Br. J. Cancer (2008)

Bottom Line: This latter group was associated with longer disease-free survivals (P=0.007) and longer time to disease-specific deaths (P=0.004).Log-rank analyses showed that molecularly positive margins were associated with shorter time to local recurrences and disease-specific deaths (P=0.03 and 0.01, respectively).This study demonstrated that QMSP of hypermethylated promoters in surgical margins predicted all the local recurrences in our series of HNSCC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Head and Neck Surgery, Institut Gustave-Roussy, 39, Rue Camille Desmoulins, Villejuif 94805, France.

ABSTRACT
This study sought to determine whether the presence of hypermethylated genes in the surgical margins can predict local recurrences in head and neck squamous cell carcinomas (HNSCCs). We prospectively collected tumour and surgical margin specimens from patients with HNSCCs who had undergone surgical resections. Quantitative methylation-specific PCR (QMSP) of CDKN2A, CCNA1 and DCC were performed in these specimens and correlated with clinical data. Of the 42 patients eligible for the study, 27 were hypermethylation informative for the above three genes. This latter group was associated with longer disease-free survivals (P=0.007) and longer time to disease-specific deaths (P=0.004). Multivariate analyses confirmed hypermethylation non-informative tumours as an independent prognosticating factor for disease-specific deaths (risk ratio 3.8, P=0.026). Quantitative MSP of the margins of 24 hypermethylation informative tumours revealed that 11 patients had molecularly positive margins, of which, five developed disease-specific events (DSEs, three local recurrences and two metastases), compared to none in patients with molecularly negative margins, after a median follow-up of 48 months. Log-rank analyses showed that molecularly positive margins were associated with shorter time to local recurrences and disease-specific deaths (P=0.03 and 0.01, respectively). This study demonstrated that QMSP of hypermethylated promoters in surgical margins predicted all the local recurrences in our series of HNSCC patients. We have also identified hypermethylation non-informative tumours as an independent predictor for the development of DSEs.

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Related in: MedlinePlus

Kaplan–Meier curve of hypermethylation informative tumour vs hypermethylation non-informative tumour in (A) disease-free survival and (B) time to disease-specific death.
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fig1: Kaplan–Meier curve of hypermethylation informative tumour vs hypermethylation non-informative tumour in (A) disease-free survival and (B) time to disease-specific death.

Mentions: Quantitative MSP of the three selected genes CDKN2A, CCNA1 and DCC was performed on 42 tumours. High levels of hypermethylation (WTMI ⩾5%, range 5.1–95%) were detected in one or more of the three genes in 64.3% (n=27/42) of tumours. These were designated as hypermethylation informative as described (Materials and Methods). Baseline clinical characteristics such as age, sex, site, stage, histopathological gravity signs and adjuvant therapy did not differ significantly according to the tumour methylation profiles (Table 1). The median clinical follow-up period was 48 months (range, 1–89). Only three patients were lost to follow-up within 24 months of diagnosis. Mean follow-up period for patients who remained events free were 70 months. Sixteen patients developed one or more disease-specific events (DSEs, defined as local and/or regional recurrences and/or distant metastasis) with median DFS of 12.25 months (range, 1–53). The hypermethylation informative group fared better, compared to the non-informative group; with longer DFSs and longer time to disease-specific deaths (P=0.007 and 0.004, respectively, Kaplan–Meier analysis with log-rank test) as shown in Figure 1. Multi-covariate analyses with possible confounding factors such as age, sex, site, stage, histopathological gravity signs and adjuvant therapy identified hypermethylation non-informative tumours as an independent prognosticating factor for DFS with a risk ratio of 3.82 (Table 2).


Quantitative methylation analyses of resection margins predict local recurrences and disease-specific deaths in patients with head and neck squamous cell carcinomas.

Tan HK, Saulnier P, Auperin A, Lacroix L, Casiraghi O, Janot F, Fouret P, Temam S - Br. J. Cancer (2008)

Kaplan–Meier curve of hypermethylation informative tumour vs hypermethylation non-informative tumour in (A) disease-free survival and (B) time to disease-specific death.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2480979&req=5

fig1: Kaplan–Meier curve of hypermethylation informative tumour vs hypermethylation non-informative tumour in (A) disease-free survival and (B) time to disease-specific death.
Mentions: Quantitative MSP of the three selected genes CDKN2A, CCNA1 and DCC was performed on 42 tumours. High levels of hypermethylation (WTMI ⩾5%, range 5.1–95%) were detected in one or more of the three genes in 64.3% (n=27/42) of tumours. These were designated as hypermethylation informative as described (Materials and Methods). Baseline clinical characteristics such as age, sex, site, stage, histopathological gravity signs and adjuvant therapy did not differ significantly according to the tumour methylation profiles (Table 1). The median clinical follow-up period was 48 months (range, 1–89). Only three patients were lost to follow-up within 24 months of diagnosis. Mean follow-up period for patients who remained events free were 70 months. Sixteen patients developed one or more disease-specific events (DSEs, defined as local and/or regional recurrences and/or distant metastasis) with median DFS of 12.25 months (range, 1–53). The hypermethylation informative group fared better, compared to the non-informative group; with longer DFSs and longer time to disease-specific deaths (P=0.007 and 0.004, respectively, Kaplan–Meier analysis with log-rank test) as shown in Figure 1. Multi-covariate analyses with possible confounding factors such as age, sex, site, stage, histopathological gravity signs and adjuvant therapy identified hypermethylation non-informative tumours as an independent prognosticating factor for DFS with a risk ratio of 3.82 (Table 2).

Bottom Line: This latter group was associated with longer disease-free survivals (P=0.007) and longer time to disease-specific deaths (P=0.004).Log-rank analyses showed that molecularly positive margins were associated with shorter time to local recurrences and disease-specific deaths (P=0.03 and 0.01, respectively).This study demonstrated that QMSP of hypermethylated promoters in surgical margins predicted all the local recurrences in our series of HNSCC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Head and Neck Surgery, Institut Gustave-Roussy, 39, Rue Camille Desmoulins, Villejuif 94805, France.

ABSTRACT
This study sought to determine whether the presence of hypermethylated genes in the surgical margins can predict local recurrences in head and neck squamous cell carcinomas (HNSCCs). We prospectively collected tumour and surgical margin specimens from patients with HNSCCs who had undergone surgical resections. Quantitative methylation-specific PCR (QMSP) of CDKN2A, CCNA1 and DCC were performed in these specimens and correlated with clinical data. Of the 42 patients eligible for the study, 27 were hypermethylation informative for the above three genes. This latter group was associated with longer disease-free survivals (P=0.007) and longer time to disease-specific deaths (P=0.004). Multivariate analyses confirmed hypermethylation non-informative tumours as an independent prognosticating factor for disease-specific deaths (risk ratio 3.8, P=0.026). Quantitative MSP of the margins of 24 hypermethylation informative tumours revealed that 11 patients had molecularly positive margins, of which, five developed disease-specific events (DSEs, three local recurrences and two metastases), compared to none in patients with molecularly negative margins, after a median follow-up of 48 months. Log-rank analyses showed that molecularly positive margins were associated with shorter time to local recurrences and disease-specific deaths (P=0.03 and 0.01, respectively). This study demonstrated that QMSP of hypermethylated promoters in surgical margins predicted all the local recurrences in our series of HNSCC patients. We have also identified hypermethylation non-informative tumours as an independent predictor for the development of DSEs.

Show MeSH
Related in: MedlinePlus