Cathepsin expression in oral squamous cell carcinoma: relationship with clinicopathologic factors.
OBJECTIVE
Proteases are involved in the invasion and metastasis of carcinoma cells. In vivo, oral carcinoma cells easily invade the bone tissue and metastasize to the submandibular and neck lymph nodes. Cathepsin expression has been shown in some neoplastic tissues and serves as a prognostic indicator. The purpose of this study was to investigate the relationship between clinicopathohistologic grades and cathepsin expressions in oral squamous cell carcinoma and to investigate which cathepsin provides prognostic information for patients with oral carcinoma.


METHODS
Immunohistochemical studies were performed on 78 carcinoma samples with monoclonal antibodies against cathepsins B, H, and L, and a polyclonal antibody against cathepsin D. Serial sections were stained by hematoxylin-eosin staining and classified by Anneroth's classification. Cathepsin B, H, L and D activities of blood serum were determined. Positive results indicative of the presence of cathepsin were investigated to determine any correlation between a particular cathepsin and histologic malignancy grades, tumor cell growth, serum cathepsin activities, and clinical factors.


RESULTS
Cathepsins B, H, L, and D were positive in every case. Although the labeling indices for cathepsins B (CB-LI), H (CH-LI), and D (CD-LI) for the cancer cases showed significant differences from those of controls, cathepsin L (CL-LI) of cancer cases showed no difference from that of controls (P <.05). A close correlation was found between CD-LI and T categories of TNM classification (P <.05), and between CD-LI and PCNA-LI (P <.05). Furthermore, a close correlation was found between CD-LI and N categories in TNM classification (P <.05). Pathologically, a close correlation was found between CB-LI or CD-LI and the pattern and/or stage of invasion (P <.05).


CONCLUSIONS
Cathepsin D and B expression were closely correlated with carcinoma invasion and progression. These proteases may be useful in determining the prognoses of patients with oral carcinoma.
Kawasaki
Goro
G
The First Department of Oral and Maxillofacial Surgery, Nagasaki University, Japan. gkawa@net.nagasaki-u.ac.jp
Kato
Yuzo
Y
Mizuno
Akio
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D002401:Cathepsin B / Q000032:analysis / Q000097:blood / Q000235:genetics; D002402:Cathepsin D / Q000032:analysis / Q000097:blood / Q000235:genetics; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis* / Q000097:blood / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000097:blood / Q000235:genetics; D004792:Enzyme Precursors / Q000032:analysis / Q000097:blood / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005887:Gingival Neoplasms / Q000201:enzymology / Q000473:pathology; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009060:Mouth Floor / Q000473:pathology; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D013223:Statistics as Topic; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000201:enzymology / Q000473:pathology
D014408:Biomarkers, Tumor; D004792:Enzyme Precursors; D018809:Proliferating Cell Nuclear Antigen; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534126:CTSH protein, human; D056655:Cathepsin H; D002402:Cathepsin D