Nodal metastasis and survival in oral cancer: Association with protein expression of SLPI, not with LCN2, TACSTD2, or THBS2.
BACKGROUND
Gene expression profiling revealed a strong signature predicting lymph node metastases in oral squamous cell carcinoma (OSCC). Four of the most predictive genes are secretory leukocyte protease inhibitor (SLPI), lipocalin-2 (LCN2), thrombospondin-2 (THBS2), and tumor-associated calcium signal transducer 2 (TACSTD2). This study correlates their protein expression with lymph node metastases, overall survival (OS), and disease-specific survival (DSS).


METHODS
Two hundred twelve patients with OSCC were included for protein expression analysis by immunohistochemistry.


RESULTS
SLPI expression correlates with lymph node metastases in the whole cohort, not in a subgroup of cT1 to 2N0. SLPI expression correlates with OS (hazard ratio [HR] = 0.61) and DSS (HR = 0.47) in multivariate analysis. LCN2, THBS2, and TACSTD2 show no correlation with lymph node metastases, OS, or DSS.


CONCLUSIONS
Although SLPI expression correlates with lymph node metastases, it has no additional value in determining lymph node metastases in early oral cancer. However, it is an independent predictor for both OS and DSS and therefore a relevant prognostic biomarker in OSCC.
Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Rob
R
Noorlag
Department of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Petra
P
van der Groep
Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Frank K J
FK
Leusink
Department of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Sander R
SR
van Hooff
Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Michaël H
MH
Frank
Department of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Stefan M
SM
Willems
Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
Robert J J
RJ
van Es
D000209:Acute-Phase Proteins / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D015815:Cell Adhesion Molecules / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics*; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012189:Retrospective Studies; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics*; D012680:Sensitivity and Specificity; D019699:Thrombospondins / Q000235:genetics*; D000099262:Thrombospondin 2
D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D053481:Secretory Leukocyte Peptidase Inhibitor; D019699:Thrombospondins; D000099262:Thrombospondin 2; C489506:LCN2 protein, human; C506814:SLPI protein, human; C499380:TACSTD2 protein, human
immunohistochemistry; lymph node metastases; oral cancer; secretory leukocyte protease inhibitor (SLPI); survival