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THE EXPRESSION OF CD98 CLINICAL RELEVANCE IN PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER ESOPHAGECTOMY
Chih-Cheng Hsieh^*1,2, Yann-Jang Chen^3,4
1Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; ²Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan; ³Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan; ⁴Department of Pediatrics, Renai Branch, Taipei City Hospital, Taipei, Taiwan

Background:
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant disease and esophagectomy is still the main treatment method. There were only several valuable and convenient markers for the detection or prediction of the disease progression and outcome, but low sensitivity of the markers limited the practice use. CD98 is a single-transmembrane glycoprotein, which has two main functions, the transportation of amino acids and regulation of some cell functions by binding to the cytoplasmic tail by β-integrin. CD98 had been reported to be a prognostic factor in many different cancers. However, these were only fewer reports in patients with ESCC. The aim of this study is to evaluate the expressions of CD98 in patients with ESCC and assessed their clinical relevance.
Material and methods:
Patients with ESCC who received esophagectomy with reconstruction between 1996 and 2011 were enrolled in this retrospective study. Those who had received preoperative chemoradiotherapy or death within 30 days after surgery were excluded. The clinicopathological information were collected. Tumor staging was classified according to the 7^th edition of AJCC cancer staging system. Expression of CD98 in paraffin embedded tumor samples were analyzed by immunohistochemistry staining and scored with a semi-quantitative method. According the expression of CD98, the patients were grouped as low and high expression subgroups. The CD98 expression, clinicopathological parameters and the survival between these two subgroups were analyzed and compared.
Results:
There were 142 males and 13 females with a mean age of 64.2 years (range 36-88 years). According to the assessment of the immunohistochemical staining, 107 (69.0%) patients had CD98 high expression in tumor tissue and the other 48 patients had low expression of CD98, that included 5 patients had no expression in tumor tissue. There were no significant correlations between clinicopathological parameters and the expression of CD98 except perineural invasion. The median follow-up time was 22.7 months (IQR: 10.7-67.4 months). There were 96 patients with tumor recurrence or metastasis. The 3-year and 5-year disease-free survival (DFS) rate were 36.5% and 32.1%, respectively. Patients with less invasive depth, nodal free status, early pathological stage, short tumor length and no lymphovascular invasion had a better DFS, but CD98 expression did not influence the DFS (p=0.393) (Table 1). The 3-year and 5-year overall survival rate were 36.1% and 27.6%, respectively. Patients with nodal free status and early pathological stage had a better OS, but CD98 expression also did not influence the OS (p=0.210) (Table 1).
Conclusions:
Different with other cancers, CD98 had a high expression percentage in surgical specimens in this study, but there was not significantly associated with prognosis.

Table 1 The survival analysis of prognostic factors influencing disease free survival and overall survival after esophagectomy

Variable		Number	Disease free survival		Overall survival
			5-year survival rate (%)	p value	5-year survival rate (%)	p value
CD98				0.393		0.210
	low	48	39.4		35.4
	high	107	28.6		24.2
Gender				0.389		0.651
	male	142	31.5		26.6
	female	13	40.0		38.5
Size				0.048		0.213
	<4cm	77	38.4		32.3
	>4cm	78	25.7		23.1
T status				0.015		0.090
	T1-2	36	51.1		41.3
	T3-4	119	26.3		23.5
N status				<0.001		0.001
	N0	56	52.7		46.2
	N1-3	99	20.7		17.2
Pathological stage				<0.001		<0.001
	I-II	60	59.3		49.8
	III-IV	95	14.6		13.7
Lymphovascular invasion				0.010		0.509
	no	123	37.8		30.0
	yes	32	12.1		18.8
Perineural invasion				0.605		0.311
	no	140	30.8		25.6
	yes	15	42.9		46.7
Post-op treatment				0.110		0.592
	no	91	37.0		29.5
	yes	64	25.5		25.0

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