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Association of trypsin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma
Author(s) -
Yamamoto Hiroyuki,
Iku Shouhei,
Itoh Fumio,
Tang Xiufen,
Hosokawa Masao,
Imai Kohzoh
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20010401)91:7<1324::aid-cncr1135>3.0.co;2-2
Subject(s) - trypsin , carcinoma , metastasis , medicine , pathology , immunostaining , esophagus , epidermoid carcinoma , cancer , gastroenterology , cancer research , immunohistochemistry , biology , enzyme , biochemistry
BACKGROUND Overexpression of the matrix serine proteinase (MSP) trypsin has been implicated in tumor growth, invasion, and metastasis. The objective of this study was to clarify the clinicopathologic and prognostic significance of trypsin expression in esophageal squamous cell carcinomas (SCC). METHODS Production of trypsin in tissue extracts was analyzed by immunoblotting and gelatin zymography. The authors analyzed the association between immunohistochemically detected trypsin expression in esophageal SCC and clinicopathologic characteristics, and they investigated whether trypsin is a predictor of recurrence and/or survival. RESULTS Overproduction and activation of trypsin was observed in 6 of 10 tumor extracts. The trypsin immunoreactivities at the invasive front were more intense than those at the superficial layer. Sections with immunostaining signals in greater than 30% of carcinoma cells at the invasive front, which were observed in 52 (52%) cases, were judged to be positive for trypsin. Trypsin positivity was significantly correlated with the depth of invasion ( P < 0.0001), lymph node metastasis ( P = 0.0048), advanced pTNM classification ( P = 0.0006), recurrence ( P = 0.0003), and recurrence within the first postoperative year ( P = 0.0005). Patients with trypsin positive carcinoma had significantly shorter disease free and overall survival times than did those with trypsin negative carcinoma ( P < 0.0001 and P < 0.0001, respectively). Trypsin retained its significant predictive value for disease free and overall survival in multivariate analysis that included conventional clinicopathologic factors ( P = 0.0029 and P = 0.0006, respectively). Patients with concomitant overexpression of trypsin and matrilysin at the invasive front, in which they often were colocalized, had the worst prognosis. CONCLUSIONS The authors' results suggest that trypsin plays a key role in the progression of esophageal carcinoma. Detection of trypsin expression as well as matrilysin is useful for the prediction of recurrence and poor prognosis. Cancer 2001;91:1324–31. © 2001 American Cancer Society.