Tissue Inhibitor of Matrix Metalloproteinase-2 in Nasopharyngeal Carcinoma

Abstract

By regulating matrix metalloproteinase (MMP) activity and controlling the breakdown of extracellular matrix components, tissue inhibitors of metalloproteinases (TIMPs) play an important role in the process of tumor invasion and metastasis. The present study was designed to clarify the role of TIMP-2 in nasopharyngeal carcinoma (NPC) patients and to evaluate its importance relative to clinicopathologic parameters. It was carried out in 30 patients with NPC and 20 controls. Tissue biopsies were studied and graded pathologically, and Western blot analysis was performed to assess TIMP-2 protein expression. Clinically, in accordance with TNM classification (T: tumor size, N: lymph node involvement, M: distant metastasis), 8 cases were diagnosed as stage II, 12 as stage III, and 10 cases as stage IV; however, pathologic typing with use of the World Health Organization (WHO) classification revealed the presence of 9 specimens of squamous cell carcinoma (WHO type 1), 6 cases of nonkeratinizing carcinoma (WHO type 2), and 15 cases of undifferentiated carcinoma (WHO type 3). The difference in percentage of TIMP-2 positivity between NPC patients (76.6%) and normal controls (30%) was statistically highly significant (P < .01). In addition, there was a significant positive correlation between TIMP-2 protein positivity and either the clinical staging or the histopathologic typing (P < .01) using Chi-square test (x²), suggesting that TIMP-2 can be used as a marker of the severity of NPC.

Accordingly, we can assume that TIMP-2 may play a role in regional lymph node and/or distant metastasis and in progression of squamous cell carcinoma. Further studies are needed to investigate the role of TIMP-2 as a marker for tumor progression and to evaluate its potential value in the follow-up of patients.

Readers are encouraged to respond to Paul Blumenthal, MD, Deputy Editor of MedGenMed, for the editor's eyes only or for possible publication via email: pblumen@stanford.edu

Cite this: Tissue Inhibitor of Matrix Metalloproteinase-2 in Nasopharyngeal Carcinoma - Medscape - Jul 03, 2007.

Clinical and Histopathologic Categorization of Nasopharyngeal Carcinoma Cases
Clinical Staging		Histopathologic Typing
Stage II	8 (26.7%)	WHO type 1	9 (30%)
Stage III	12 (40%)	WHO type 2	6 (30%)
Stage IV	10 (33.3%)	WHO type 3	51 (50%)

Stage II (T₂N₀M₀)
Stage III (T₃N₀M₀-T_1,2 or₃,N₁M₀)
Stage IV (T₄N₀M₀-any T,N₂ or N₃,.M₀-any T, any N,M₁)
T1: Tumor confined to 1 site or no tumor visible
T2: Involving 2 sites (both posterosuperior and lateral wall)
T3: Extension into nasal cavity or oropharynx
T4: Tumor invasion of skull or cranial nerve involvement (or both)
N1: Metastasis in a single ipsilateral lymph node < 3 cm
N2: Metastasis in contralateral, bilateral, multiple lymph nodes or > 3 cm but < 6 cm
N2: Metastasis in lymph nodes > 6 cm
M0: No distant metastasis
M1: Distant metastasis.
WHO type 1: Squamous cell carcinoma
WHO type 2: Nonkeratinizing carcinoma
WHO type 3: Undifferentiated carcinoma that is lymphoepithelioma and anaplastic carcinoma

Percent Positivity of TIMP-2 Protein: Comparison Between Nasopharyngeal Carcinoma Patients and Controls
Positivity of TIMP-2	Malignant Cases	Controls
	23/30	6/20
	76.6%	30%
Pearson's Chi-squared test (x²)	9.1
P-value	< .01*

*Highly significant

TIMP-2 Protein Positivity in Relation to Clinical Staging and Histopathologic Typing
TIMP-2	Histopathologic Typing				Clinical Staging
		Stage II	Stage III	Stage IV	WHO 1	WHO 2	WHO 3
	(-)	4	3	0	4	2	3
	(+)	4 (50%)	9 (75%)	10 (100%)	5 (44.4%)	3 (60%)	12 (80%)
Pearson's Chi-squared test (x²)	9.3				9.1
P* value	< .01				< .01

*P < .01 = highly significant

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Tissue Inhibitor of Matrix Metalloproteinase-2 in Nasopharyngeal Carcinoma

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