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. 2009 Jun;18(2):81-7.
doi: 10.1097/PDM.0b013e3181804b82.

Noninvasive molecular detection of head and neck squamous cell carcinoma: an exploratory analysis

Seema Sethi  1 , Michael S Benninger, Mei Lu, Shalita Havard, Maria J Worsham
Affiliations

Noninvasive molecular detection of head and neck squamous cell carcinoma: an exploratory analysis

Seema Sethi et al. Diagn Mol Pathol. 2009 Jun.

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease evolving through multistep carcinogenesis, one of the steps being genetic alterations. Noninvasive identification of HNSCC-specific genetic alterations using saliva would have immense potential in early diagnosis and screening, particularly among high-risk patients.

Design: In this exploratory study, a prospective cohort of 27 HNSCC and 10 healthy controls was examined to determine whether genetic alterations (losses and gains) in saliva DNA differentiated HNSCC patients from normal controls. Saliva DNA was interrogated by a candidate gene panel comprising 82 genes using the multiplex ligation-dependent probe amplification assay.

Results: Eleven genes showed some predictive ability in identifying HNSCC cases from normal controls: PMAIP1, PTPN1, ERBB2, ABCC4, UTY, DNMT1, CDKN2B, CDKN2D, NFKB1, TP53, and DCC. Statistical analysis using the Classification and Regression Tree (CART) identified 2 genes, PMAIP1 and PTPN1, which correctly discriminated all 27 HNSCC patients (100%) from normal controls. Results were validated using the leave-one-out validation approach.

Conclusions: Noninvasive high-throughput multiplex ligation-dependent probe amplification identified discrete gene signatures that differentiated HNSCC patients from normal controls providing proof-of-concept for noninvasive HNSCC detection.

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Figures

Figure 1
Figure 1
Saliva MLPA: gain of PMAIP1 and PTPN1 genes seen in HNSCC case 14 compared to normal control.
Figure 2
Figure 2
CART statistical analysis: Starting with 37 study subjects (Node1; blue box), gain of PMAIP1 gene partitioned 21 HNSCC patients (Node 3; red box); gain of PTPN1 gene separated the remaining 6 HNSCC patients ( terminal Node 2; red box) from all 10 normal controls (terminal Node 1; red box).
Figure 3
Figure 3
PMAIP1 and PTPN1 gene status: all HNSCC patients (black dots) showed gain (>2) of one/both genes, quadrants 2, 3 and 4; 27 observations; in contrast to <2 seen in normal controls (red dots) in quadrant 1; 10 observations.
See this image and copyright information in PMC

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