Journal of Pathology and Translational Medicine

Volume 38(2); April 2004

Original Articles

Expression of Matrix Metalloproteinase-2 (MMP-2) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) in Pancreatic Ductal Adenocarcinoma.: Mi Jin Gu, Young Kyung Bae, Joon Hyuk Choi; Korean J Pathol. 2004;38(2):73-78.

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Abstract PDF: BACKGROUND
Matrix metalloproteinase-2 (MMP-2) is known to be one of the key molecules for tumor invasion and metastasis. MMP-2 activity is modulated through interaction with the tissue inhibitor of metalloproteinase-2 (TIMP-2). The purpose of this study was to evaluate the expression of MMP-2 and TIMP-2 in pancreatic ductal adenocarcinoma.
METHODS
Using immunohistochemical staining, we investigated the expression of MMP-2 and TIMP-2 in 30 pancreatic ductal adenocarcinomas and 10 normal pancreas.
RESULTS
MMP-2 expression was present in tumor cells in 11 cases, and in stromal cells in 24 cases, out of 30 carcinomas. MMP-2 expression of tumor cells was significantly higher in poorly differentiated adenocarcinomas than in well/moderately differentiated adenocarcinomas, and in cases with vascular invasion than in cases without. MMP-2 expression was stronger in the marginal areas than in the central area of the tumor. TIMP-2 expression was detected in the tumor and stromal cells of all carcinomas. MMP-2 and TIMP-2 expression had no significant correlation with tumor size, lymph node metastasis, or TNM stage. MMP-2 expression was not correlated with TIMP-2 expression.
CONCLUSIONS
These results suggest that MMP-2 expression may play an important role in the invasive property of pancreatic ductal adenocarcinoma, whereas TIMP-2 expression increases as a reaction to invasion.

MMP-2 and MMP-9 Expressions in Breast Carcinomas and Relationship with Major Prognostic Factors.: Hye Kyoung Yoon, Seol Mi Park; Korean J Pathol. 2004;38(2):79-85.

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Abstract PDF: BACKGROUND
MMP-2 and MMP-9 are involved in the degradation of extracellular matrix, and MMP-2 and MMP-9 expressions in breast carcinomas have been reported as a poor prognostic factor. The aim of this study is to evaluate the prognostic value and the regulatory factors of MMP-2 and MMP-9 expressions in 73 cases of infiltrating ductal carcinomas, NOS type.
METHODS
Immunohistochemistry for MMP-1, -2, -3, -9 and TIMP-1, -2 were performed and evaluation for patient? age, size, histologic grade, lymph node metastasis and tumor markers such as ER, PR, p53, c-erbB-2, cathepsin D, MIB-1, and microvessel density was done.
RESULTS
The expression rates of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2 were 74.0%, 76.7%, 1.4%, 87.7%, 24.7% and 75.3%, respectively. MMP-2 expression rate was higher in the tumors of low and intermediate grade and PR positive tumors (p<0.05), and MMP-9 expression showed an increasing tendency in ER positive tumor (p=0.0676). Positive relationships between MMP-2 and MMP-1 expressions, and MMP-9 and TIMP-2 expressions were recognized (p<0.05).
Conclusion
: The prognostic significance of MMP-2 and MMP-9 expressions is still unclear, and MMP-2 and MMP-9 expressions seemed to be positively related with MMP-1 and TIMP-2 expression, respectively.

Nitric Oxide Synthase Expression in Early Stage of Aging Rat Kidney.: Kye Won Kwon, Hyeon Joo Jeong; Korean J Pathol. 2004;38(2):86-92.

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Abstract PDF: BACKGROUND
Nitric oxide synthase (NOS) has been suggested to have a role in renal injury of aging rats.
METHODS
Renal function and histology were compared between 12 month-and 7-9 week-old rats. Proliferating activity and cell death were evaluated by PCNA index and apoptosis. Three isoforms of NOS (eNOS, iNOS, and nNOS) were stained by immunohistochemistry.
RESULTS
Serum creatinine level was increased in old rats (1.0 mg/dL vs 0.5 mg/dL, p=0.000). 24 h proteinuria and urinary NO were comparable between the two groups. The percentage of global and segmental glomerulosclerosis increased in old rats. PCNA index decreased in the glomeruli (0.1 vs 0.6/glomerulus, p=0.005) and the tubulointerstitium (10.2 vs 19.2/mm2, p=0.019) of old rats compared to that of young rats. However, no difference was observed in the number of TUNEL positive cells. eNOS was not stained in young and old rat kidney, whereas iNOS was stained in the interstitial inflammatory cells of old rats (0.3 vs 0.0 of young rats/mm2, p=0.188). Macula densa nNOS staining significantly decreased in old rats compared to young rats (5.6 vs 9.5/mm2, p=0.009).
CONCLUSIONS
Proliferating activity is more affected than cell death with aging. Decreased nNOS expression without alteration of eNOS and iNOS expressions may implicate nNOS as a marker of renal injury in the early stage of aging.

Clinicopathologic Significance of CD44s, CD44v5 and CD44v6 Expression in Non Small Cell Lung Carcinomas.: Jae Kyun Kim, Chang Hun Lee, Kyeong Min Lee, Jin Mi Song; Korean J Pathol. 2004;38(2):93-99.

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Abstract PDF: BACKGROUND
CD44 is a polymorphic family of transmembrane glycoproteins generated by alternative splicing of messenger RNA and is involved in the mechanism of tumor invasion and metastasis.
METHODS
The expression of selected CD44 molecules (CD44s, CD44v5, and CD44v6) was determined immunohistochemically in 84 cases of non small cell lung carcinomas (NSCLCs). The results were compared with PCNA index, microvessel density (MVD), and clinicopathological parameters including patient? survival.
RESULTS
CD44s showed a positive reaction in 61.9% (52/84) of NSCLCs, CD44v5 in 73.8% (62/84), and CD44v6 in 39.3% (33/84). Squamous cell carcinomas (SCCs) displayed preferential expression of all CD44 molecules in comparison with adenocarcinomas (ACs) (p<0.001). As a whole, the expression of CD44 molecules was not correlated with clinical parameters (stage, TNM-T, and TNM-N), PCNA index, or MVD. For ACs only, however, CD44v5 expression was negatively correlated with PCNA index (p<0.05). Poor survival was correlated with CD44v5 expression in ACs and CD44v6 in SCCs (both, p<0.05).
CONCLUSIONS
These findings suggest that CD44 molecule in NSCLC could be a distinctive phenotypic marker for SCC, and the possibility that CD44v5 and CD44v6 are in some way instrumental in conditioning the biologic behavior of NSCLC according to major histologic types.

The Relationship between PTEN Tumor Suppressor Gene and Vascular Endothelial Growth Factor-Mediated Angiogenesis in Breast Cancer.: Jean Kyung Park, Min Jung Jung, Bong Kwon Chun, Bang Hur; Korean J Pathol. 2004;38(2):100-105.

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Abstract PDF: BACKGROUND
PTEN is a novel tumor suppressor gene located at chromosome 10q23.3. Loss of PTEN function has been implicated in the progression of several types of cancer. Angiogenesis is a critical factor in tumor growth and metastasis. We investigated PTEN expression in invasive breast cancers and described its role in the regulation of angiogenesis related to vascular endothelial growth factor (VEGF).
METHODS
Forty-five, surgically resected, formalin-fixed and paraffin embedded breast cancer tissue samples were analyzed for PTEN and VEGF expressions by immunohistochemistry and for microvessel density (MVD) by CD34 immunostaining.
RESULTS
Loss of PTEN expression was found in 35.6% (16/45) of the breast cancer tissues, all of which showed positive VEGF expression. Among 29 cases with normal PTEN expression, 15 (51.7%) were VEGF positive. MVD was significantly higher in tumors with a loss of PTEN expression than in those with normal PTEN expression.
CONCLUSION
A loss of PTEN expression might increase the VEGF-related angiogenesis in breast cancer. There was no correlation between PTEN expression and clinicopathologic parameters. Detection of the loss of PTEN expression may serve as a useful biologic marker for progression in invasive breast cancer.

Case Reports

Giant Multilocular Cystadenoma of the Prostate: A Case Report.: Chang Ohk Sung, Jinwon Seo, Sang Yong Song; Korean J Pathol. 2004;38(2):106-108.

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Abstract PDF: Large multilocular cysts and cystic neoplasms of the prostate are very rare. A healthy 52-year-old man presented with acute urinary retension. Physical examination revealed a large abdominal mass. Pelvic MRI showed a 15x10x9 cm, lobulated, and multiseptated cystic mass in the pelvic cavity. Exploration laparotomy revealed a large cytic mass that compressd and displaced the urinary bladder antero-laterally, and adhered to the prostate and the sigmoid colon. Macroscopically, the mass was grayish white colored, multilocular cysts containing reddish-brown serous fluid. Microscopically, the tumor was composed of glands and cysts lined by the prostatic-type epithelium in the fibrous stroma. The prostatic nature of the lesion was confirmed by the lining epithelium expressing prostate-specific antigen.

Primary Carcinoid Tumor of the Uterine Corpus: A Case Report.: Sung Ran Hong, Hy Sook Kim, Jae Uk Shim; Korean J Pathol. 2004;38(2):109-112.

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Abstract PDF: Carcinoid tumors of the female genital tract are an uncommon clinical finding. This study presents a case of typical carcinoid tumor of the uterine corpus in a 61-year-old woman. The tumor was a primary carcinoid tumor arising from the endometrium which showed the typical organoid patterns with a positive reaction for neuroendocrine markers. The patient was treated by a total hysterectomy and bilateral salpingo-oophorectomy. No evidence for the carcinoid syndrome was noted. The carcinoid tumor recurred as a vaginal mass approximately six and a half years later. The patient died from a mechanical intestinal obstruction by the carcinoid tumor with distant metastasis approximately eight and a half years after operation of the endometrial primary tumor.

Conjunctival Pigmented Actinic Keratosis: A Case Report.: Jinyoung Yoo, Ji Han Jung, Hyun Joo Choi, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2004;38(2):113-115.

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Abstract PDF: We recently had a case of pigmented actinic keratosis arising in the conjunctiva, and this is an unusual site for the lesion. Most actinic keratoses are seen on sun-exposed areas of the skin, especially for Caucasians living in sunny climates. When these lesions are pigmented, they may resemble lentigo maligna. A 56-year-old man was referred to the ophthalmology clinic for a pigmented conjunctival lesion. An ophthalmologic examination revealed multiple dark brown-colored, linear or irregular shaped patches located on the lateral side of the conjunctiva in his right eye, partially covering the cornea, and this made a clinical differentiation from other possible pigmented lesions somewhat difficult. A histologic examination of the subsequent biopsy specimen demonstrated acanthosis with melanocytes containing heavy melanin, scattered dyskeratotic cells, atypical keratinocytes, and solar elastosis, and all of their findings are consistent with pigmented actinic keratosis.

Odontogenic Gingival Epithelial Hamartoma; with Reference to the Expression of Ameloblastin Gene by in situ Hybridization and Immunohistochemistry.: Na Rae Kim, Yeon Lim Suh, Je G Chi, Young Joon Lee, Suk Keun Lee, Jae Il Lee, Chang Yun Lim, Ji Young Park; Korean J Pathol. 2004;38(2):116-120.

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Abstract PDF: Odontogenic gingival epithelial hamartoma (OGEH) is an extremely rare lesion characterized by an abnormal proliferation of odontogenic epithelium. This lesion is thought to arise from the rest of the dental lamina lying dormant in the gingival tissue after odontogenesis. Distinguishing OGEH from the granular cell variant of ameloblastoma and central odontogenic fibroma is important. To date, only eleven cases have been reported, and its pathogenesis remains unclear. We report here on a case of OGEH, where the epithelial strands in the lesion were conspicuously positive for the antisera of cytokeratin 19 and ameloblastin. Tumor cells intensely expressed ameloblastin mRNA by in situ hybridization. To the best of our knowledge, this is the first case of OGEH to which ameloblastin immunohistochemical stain and in situ hybridization were applied. Although our study is limited to a single case, the coexpression of cytokeratin 19 and ameloblastin might indicate the origin and specific cytodifferentiation of OGEH is quite different and unique, when contrasted to other odontogenic tumors.

Minimal Deviation Adenocarcinoma, Mucinous Type, of the Uterine Cervix: Report of a Case with Extensive Metastasis to the Uterine Corpus and Bilateral Adnexae.: Eundeok Chang, Eunjung Lee, Kyoungmee Kim, Okran Shin, Youngmi Ku, Heejung An, Changsuk Kang; Korean J Pathol. 2004;38(2):121-125.

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Abstract PDF: Minimal deviation adenocarcinoma is an extremely well differentiated variant of cervical adenocarcinoma, and is frequently misdiagnosed due to its benign-looking histopathological features. A 38-year-old woman was diagnosed as having had a minimal deviation adenocarcinoma in the cervix, metastasizing to the uterine body and bilateral adnexae. She had a history of right salpingo-oophorectomy 3 years ago, and was diagnosed as having a mucinous cystadenoma. Histologically, the tumor cells were so well-differentiated that they appeared to be almost the same as those of the non-neoplastic cervical glands. Similar glands were found in both ovaries and in the left fallopian tube. PAS staining showed a negative or apical positive pattern in the endocervical-like glands. Immunohistochemical studies for CEA, ER/PR, cytokeratin 20, and p53 were negative, but positive for cytokeratin 7. The HPV DNA microarray test was negative. Clinically, this proved to be an advanced, biologically aggressive disease.

Mucous Gland Adenoma Presenting as a Peripheral Lung Mass: A Brief Case Report.: Ji Eun Kwon, Gou Young Kim, Joungho Han, Tae Sung Kim, Kwanmien Kim; Korean J Pathol. 2004;38(2):126-128.

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Abstract PDF: Mucous gland adenoma (MGA) of the lung is an uncommon, benign tumor that histologically resembles the mucus-secreting component of the tracheobronchial gland. The majority arises within the main, lobar or segmental bronchi. MGA presenting as a peripheral lung mass is extremely rare. We herein report a case of MGA that uniquely arose from the peripheral territory of the superior segmental bronchus of the left lower lobe in a 73-year-old male. Chest computed tomography showed a 13 mm-sized, subpleural nodule, which was easily enucleated by video-assisted thoracotomy. The mass was round and gray-tan in color with mucoid material. The tumor was composed of cysts, tubules, and glands lined by bland columnar, cuboidal or flattened, mucus secreting cells.

Solitary Fibrous Tumor of the Urinary Bladder: A Case Report.: Jong Sil Lee, Jeong Seok Hwa, Gyung Hyuck Ko, Jeong Hee Lee, Hwal Woong Kim; Korean J Pathol. 2004;38(2):129-131.

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Abstract PDF: Solitary fibrous tumor (SFT) most commonly affects the pleura and these tumors have been recently reported to be found in unusual locations. We describe here a solitary fibrous tumor of the urinary bladder that was removed from a 79-year-old man having a history of gross hematuria and dysuria. Transabdominal ultrasonography showed a huge soft tissue mass in the urinary bladder. The cut surface of the tumor showed a grayish-white, hemorrhagic and gelatinous appearance. Necrosis was not found. Microscopically, the tumor showed a proliferation of spindle or ovoid cells that were intervened by a collagenous stroma. A variety of growth patterns was identified but the so-called patternless pattern was the predominant one. The spindle cells had almost no mitotic figures, and there was very little or no nuclear atypia. Immunohistochemical stains showed a strong reactivity for CD34 and a focal reactivity for bcl-2. The ultrastructure of the tumor cells showed mesenchymal-myofibroblastic traits.

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