Original Article

The clinical value of lymphatic vessel density, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 expression in patients with oral tongue squamous cell carcinoma ABSTRACT Background: Oral tongue squamous cell carcinoma (OTSCC) is an oral carcinoma prone to lymphatic metastasis. Intercellular adhesion molecule 1 (ICAM‑1) and vascular cell adhesion molecule 1 (VCAM‑1) as important adhesion molecules play roles in regulating cell‑cell adhesion and tumor cells metastasis. Materials and Methods: Lymphatic vessel density (LVD) was evaluated by immunohistochemistry using anti‑human D2‑40 antibody. The expression of ICAM‑1 or VCAM‑1 in lymphatic vessels were measured by double immunofluorescence staining. Then both of the LVD and the expression of ICAM‑1 or VCAM‑1 were compared between in normal tongue and in OTSCC lymphatic vessels. In OTSCC, statistical analyses were performed to determine the prognostic correlation of ICAM‑1 or VCAM‑1 levels. Results: LVD and expression of ICAM‑1 or VCAM‑1 in OTSCC lymphatic vessels was higher than those in normal tongue lymphatic vessels (LVD: 21.454 ± 7.022, 8.498 ± 1.679; ICAM‑1: 30.241 ± 5.639%, 5.050 ± 1.227%; VCAM‑1: 33.134 ± 5.127%, 2.113 ± 0.446%, in OTSCC, normal tongue tissues, respectively). High LVD and high ICAM‑1 or VCAM‑1 expression in lymphatic vessels was significantly associated with lymphatic node metastasis. Overall survival was significantly shorter in patients with high LVD and ICAM‑1 or VCAM‑1 expression in lymphatic vessels. Conclusions: LVD and expression of ICAM‑1 or VCAM‑1 in OTSCC was higher than that in normal tongue lymphatic vessels. Monitoring changes in the expression of ICAM‑1 or VCAM‑1 in lymphatic vessels may be a useful technique for assessing prognoses in OTSCC patients. KEY WORDS: Immunohistochemistry, intercellular adhesion molecule 1, lymphatic vessel density, oral tongue squamous cell carcinoma, prognosis, vascular cell adhesion molecule 1

INTRODUCTION Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer diagnosed in the oral cavity comprising 25–40% of oral carcinoma.[1] Patients with OTSCC have a significantly worse prognosis than those at other oral cavity sites.[2] A rich lymphatic network and highly muscularized structure make OTSCC more frequently associated with metastasis to draining lymph nodes.[3] Lymphangiogenesis has been found in many types of primary tumor tissues, including in oral squamous carcinoma.[4‑7] The large amount and the immaturely and dysfunctionally structural characteristics of the new vessels may facilitate tumor cell’s metastasis.[8,9] Although the mechanism of tumor cell’s migration into lymphatic vessels

has not been fully illustrated, alteration in cell‑cell adhesion is essential during the metastatic pathway. [10‑12] Adhesion molecules commonly play a central role in cell‑cell adhesion, in which intercellular adhesion molecule 1 (ICAM‑1) and vascular cell adhesion molecule 1 (VCAM‑1) are the most effective molecules and are most widely studied.

Junjie Yan, Yinhua Jiang, Min Ye, Weidong Liu, Liang Feng1 Department of Stomatology, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, China, 1 Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China For correspondence: Dr. Liang Feng, Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China. E‑mail: fengliang1979@126. com

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Intercellular adhesion molecule 1, also called CD54, is a cell surface glycoprotein typically expressed on endothelial cells and immune system cells. ICAM‑1 is a ligand for LFA‑1 (integrin), a receptor found on leukocytes.[13] VCAM‑1, or known as CD106, is a cell surface sialoglycoprotein. VCAM‑1 is an endothelial ligand for VLA‑4 (or α4 β1 integrin) and α4 β7 integrin.[14] CAMs, including ICAM‑1 and VCAM‑1, physiologically have the similar function.

Journal of Cancer Research and Therapeutics - Volume 10 - Special Issue 2- 2014

Website: www.cancerjournal.net DOI: 10.4103/0973-1482.145827 PMID: *** Quick Response Code:

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Yan, et al.: Oral tongue squamous cell carcinoma

In inflammation or immune response, activated leukocytes can bind to endothelial cells via ICAM‑1/LFA‑1 or VCAM‑1/VLA‑4, then transmigrate into inflammatory tissue sites.[15,16] Until now, there have no reports of ICAM‑1 and VCAM‑1 expression on lymphangiogenesis vessels in OTSCC. In this study, first we measured lymphatic vessel density (LVD), then focusing on the expression of ICAM‑1 and VCAM‑1 in lymphatic endothelium, to investigate their relationship with OTSCC cell’ s migration and clinicopathologic parameters, in order to determine if these results can be used to assess risk of lymphatic metastasis and prognosis in patients. MATERIALS AND METHODS Patients and tumor specimens Tissue samples were collected from 80 OTSCC patients diagnosed and treated at Harbin Medical University Stomatological Hospital, Harbin, China and The People’s Hospital of Lishui, Zhejiang 323000, China, from the year 2000–2006. Before treatment, informed consent for the scientific use of tissue materials was obtained from the patients that were approved by the Local

Ethics Committee. All patients underwent potentially curative surgery without preoperative therapy. Table 1 presents the clinical and pathological characteristics of these patients. Normal oral mucosa group were obtained from each of the tissue 2.0–2.5 cm away from the primary tumor,[17] and the organization were graded according to the tissue morphology. All patients were staged according to the 1997 UICC tumor node metastasis (TNM) Classification of Malignant Tumors.[18] After treatment, all patients were followed‑up until death or for at least 60 months. All specimens were fixed routinely in 10% formalin and embedded in paraffin. Consecutive 4‑μm‑thick sections were cut and deparaffinized with xylene, rehydrated in a graded alcohol series. One section from each tumor was stained with hematoxylin and eosin to reevaluate the histologic diagnosis according to Anneroth’s classification,[19] and the other sections were used for immunohistochemistry. The grade of tumor differentiation was determined using the criteria proposed by the World Health Organization.[20] Monoclonal antibodies against D2‑40 were used as lymphatic endothelial marker to evaluate LVD in a conventional method.

Table 1: Relationship between LVD, expression of ICAM‑1, VCAM‑1 in lymphatic endothelium and clinicopathologic parameters (n=80) Clinical parameters Age 4 cm Tumor depth

The clinical value of lymphatic vessel density, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 expression in patients with oral tongue squamous cell carcinoma.

Oral tongue squamous cell carcinoma (OTSCC) is an oral carcinoma prone to lymphatic metastasis. Intercellular adhesion molecule 1 (ICAM-1) and vascula...
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