Journal of Pathology and Translational Medicine

Original Articles

Immunohistochemical Evaluation of Cathepsin D, MMP-2, and TIMP in Prostate Carcinoma.: Jung Weon Shim, Soon Ran Kim, Yun Jung Kim, Hye Kyung Ahn, Young Euy Park, Sung Sook Kim, Min Young Kim; Korean J Pathol. 1997;31(4):342-350.

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Abstract PDF: Twenty six cases of primary adenocarcinoma of the prostate, ranging from 4 to 9 according to Gleason's summing score, were studied. Immunoreactivity was evaluated using the rabbit polyclonal anti-Cathepsin D antibody (CD), a mouse monoclonal MMP-2 antibody (MMP-2), and a tissue inhibitor metalloproteinase (TIMP) in formalin-fixed, paraffin-embedded prostatic tissue. Immunohistochemical staining was scored by summing the intensity of staining (0 to 3+) weighted by the percentage of tumor staining at each intensity (H score, theoretical range 0 to 300). For CD, the tumor cells showed diffuse cytoplasmic immunoreactivity in all 26 cases (100%). For MMP-2 the tumor cells showed cytoplasmic immunoreactivity in 17 of 26 cases (65.38%). As the Gleason grade increased the expression of CD increased (P=0.0027). The reactivity of CD was significantly correlated with the Gleason's score (R=0.65637), but, the reactivity of MMP-2 was not correlated. There were no significant correlations between each of the CD and the MMP-2 scores, and stage. TIMP expression was predominantly localized in the stroma rather than in the cancer cells themselves. We believe that 1) CD and MMP-2, both immunohistochemically detectable in a majority of prostate adenocarcinoma, may play a role in determination of the invasive or metastatic property, 2) the enhanced TIMP expression in the stroma may be associated with the response to cancer invasion.

Expression of Chromogranin A, Cathepsin D, Cyclin D1 and p53 proteins in Colorectal Adenocarcinoma.: Chae Hong Suh, Mi Ja Lee, Sung Kang Cho; Korean J Pathol. 2001;35(1):7-13.

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Abstract PDF: BACKGROUND
The purpose of this study is to assess the roles of chromogranin A, cathepsin D, cyclin D1 and p53 protein expression in colorectal tumorigenesis.
METHODS
83 colorectal cancer and 12 villotubular adenoma tissue specimens were investigated by immunohistochemical staining for chromogranin A, cathepsin D, cyclin D1 and p53 protein. Clinicopathologic values (tumor size, histologic grade, Astler-Coller stage and lymph node metastasis) were compared with the incidence of chromogranin A, cathepsin D, cyclin D1 and p53 protein expression in colorectal adenocarcinomas.
RESULTS
Statistically significant correlation was noted between the expression of chromogranin A and histologic grade (p<0.05). The incidence of positive cathepsin D expression was increased with tumor size (p<0.05), and there was a statistically significant correlation between histologic grade and cathepsin D expression (p<0.005). There were no statistically significant correlations among cyclin D1 expression and tumor size, histologic grade, stage and lymph node metastasis. Patients with lymph node metastasis had a high incidence of positive p53 protein expression compared to those without this finding (p<0.001).
CONCLUSION
It is suggested that chromogranin A, cathepsin D, and p53 protein are useful variables for the prognostic assessment of colorectal adenocarcinoma. The p53 protein seems to involve the metastatic ability of colorectal adenocarcinomas. Also, the expression of cathepsin D, cyclin D1, and p53 protein may play an important role in the tumorigenesis and progression of the colorectal adenoma-carcinoma sequence.

Immunocytochemical Assay of Cathepsin D in Fine Needle Aspiration Cytology of Breast Carcinoma and Benign Breast Diseases .: Kyeongmee Park, Illhyang Ko; Korean J Cytopathol. 2000;11(2):75-81.

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Abstract PDF: Cathepsin D is a protease which is known to facilitate invasion and metastasis of breast carcinoma. Overexpression of cathepsin D is associated with poor clinical outcome and biologic aggressiveness of the breast cancer. We underwent immunocytochemical assay(ICA) for cathepsin D in fine needle aspiration cytology(FNAC) specimens from the breast carcinoma and benign breast diseases. In FNAC specimens cathepsin D was expressed in 21(42.9%) out of 49 cases of invasive ductal carcinoma, whereas negative result was observed in all 15 cases of benign breast diseases including 7 fibroadenomas, 6 fibrocystic diseases, and 2 benign ductal hyperplasias. Among the 11 FNAC specimens from ductal carcinoma in situ(DCIS), cathepsin D was expressed in 3 cases(27.3%). In FNAC specimens immunocytochemistry for cathepsin D showed positive result in 24 out of 60 carcinomas(sensitivity, 40%) and negative result in 15 out of all 15 benign breast diseases(specificity, 100%). No significant correlation was noted between cathepsin D expression in FNAC specimen and clinicohistological characteristics of the breast carcinoma, such as hormone receptors and cell differentiation. In conclusion, ICA of cathepsin D in FNAC specimens thought to be a good adjunct to differentiate malignancy from benign breast diseases.

The Difference of Cathepsin D Expression between Invasive Ductal Carcinoma and Ductal Carcinoma In Situ of the Breast.: Hye Kyoung Yoon, Soo Jin Jung; Korean J Pathol. 2004;38(6):408-414.

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Abstract PDF: BACKGROUND
It is known that cathepsin D expression in host stromal cells is associated with a more aggressive tumor behavior in breast cancers.
METHODS
Cathepsin D expression was examined in 222 cases of invasive ductal carcinoma (CA) and 25 cases of ductal carcinoma in situ (DCIS) by the immunohistochemical staining. Cathepsin D expression was evaluated according to the expression site, either in the tumor cells (CD-T) or in the stromal cells (CD-S), and graded according to the immunopositivity. The differences of CD-T and CD-S in each case were evaluated according to the pathologic parameters and estrogen receptor (ER)/progesterone receptor (PR) status.
RESULTS
The rate of CD-S was significantly higher in the CA than in the DCIS (p<0.0001). In the CA, the rate of CD-S was higher than that of CD-T, while in the DCIS, the rate of CD-T was higher than that of CD-S. In the CA, the rate of CD-S and the tumor grade showed a positive relationship (p=0.0281). There were positive correlations between the ER positivity and CD-S (p=0.0236), and between the PR positivity and CD-T (p=0.0246). For the DCIS, no significant relationships were noted between the pathologic parameters including ER/PR status and CD-T/CD-S.
CONCLUSION
Cathepsin D expression in the stromal cells seems to be related to the invasiveness and aggressive biological behavior in breast cancers. In addition, there might be some relationship betweeen the ER positivity and CD-S, and between the PR positivity and CD-T.

Relationship between Immunohistochemical Expression of Cathepsin D and Other Prognostic Factors of Breast Carcinoma.: Kwang Hwa Park, Byeng Woo Park, Kyong Sik Lee, Kwang Gil Lee; Korean J Pathol. 1994;28(6):612-619.

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Abstract PDF: The cathepsin D is a lysosomal protease secreted in excess by breast cancer cells. The function of this enzyme is degradation of the extracellular matrix and proteoglycan. It is induced by estrogens in estrogen receptor positive breast cancer cell lines. On the basis of this, cathepsin D expression in breast cancer cells seems to be correlated with the prognosis. But there is debates in its prognostic significance. Relationship between cathepsin D expression and other prognostic factors of breast cancer was studied. We investigated 51 cases of invasive ductal cell carcinoma of breast removed by open biopsy or mastectomy. All cases were fixed in formalin and embedded in paraffin. We used 46-KD intermediate form of the enzyme for cathepsin D expression on immunohistochemical stain. We observed no significant correlation with age, stage, histologic grade, lymphatic invasion, and estrogen receptor status. Cathepsin D may be an independent factor which is not related with other prognostic factors, especially estrogen receptor status.

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