Journal of Pathology and Translational Medicine

Volume 40(1); February 2006

Review

Oncogenic osteomalacia.: Yong Koo Park; Korean J Pathol. 2006;40(1):1-8.

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Abstract PDF: An unusual and rare presentation of osteomalacia results from the paracrine effect of a localized bone or soft tissue neoplasm. In this syndrome, known as tumor induced osteomalacia or oncogenic osteomalacia, a neoplasm synthesizes and secretes a circulating compound, known as phosphatonin, which acts on the kidney leading to phosphate wasting. Oncogenic osteomalacia can be caused by a wide variety of neoplasm, although they are usually primary soft tissue or bone tumors. Most commonly the causative neoplasm is a benign or low-grade malignant vascular or fibrous tissue tumor. Complete removal of the offending neoplasm completely reverses the osteomalacia. If successful, the osteomalacia resolves. However, incomplete removal of the neoplasm necessitates treatment with phosphate and Vitamin D3 to ameliorate the skeletal disease.

Original Articles

Expression of the 14-3-3 sigma Protein and Methylation Status of the 14-3-3 sigma gene in Biliary Neoplasms.: Dong Eun Song, Se Jin Jang, Jung Sun Kim, Sang Soo Lee, Myung Hwan Kim, Seung Gyu Lee, Young Joo Lee, Hae Joung Park, Yhong Hee Shim, Eunsil Yu; Korean J Pathol. 2006;40(1):9-16.

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Abstract PDF: BACKGROUND
The 14-3-3 sigma (sigma) protein has a negative regulatory role in the cell cycle progression of the. Down-regulation or overexpression of the 14-3-3 sigma protein has been reported in various human cancers.
METHODS
Immunohistochemistry for the 14-3-3 sigma protein was performed in non-neoplastic bile duct cells, intraductal papillary neoplasms of the liver (IPNL), mass-forming intrahepatic cholangiocarcinomas (ICC) and non-papillary extrahepatic cholangiocarcinomas (ECC). We investigated the methylation status of the 14-3-3 sigma gene in 45 cases of these 3 tumor groups.
RESULTS
The non-neoplastic bile duct cells demonstrated negative or weakly positive cytoplasmic immunoreactivity for the 14-3-3 sigma protein and no methylation of the 14-3-3 sigma gene. Overexpression as well as negative immunoreactivity associated with hypermethylation of the 14-3-3 sigma protein was observed in 16 (69.6%) of 23 cases of IPNL, in 21 (63.6%) of 33 cases of mass-forming ICC and in 27 (71.1%) of 38 cases of non-papillary ECC. Negative immunoreactivity was increased in the invasive IPNL (4/6, 66.7%), as well as in the poorly differentiated cases of mass-forming ICC (8/12, 66.7%) and the non-papillary ECC (5/8, 62.5%).
CONCLUSIONS
The similar rates for the abnormal expression of the 14-3-3 sigma protein among the three groups of biliary neoplasms indicate its general association with biliary carcinogenesis. Furthermore, the loss of the 14-3-3 sigma protein may be involved in the tumor progression and differentiation in the biliary carcinogenesis.

Expressions of CD44s Is Associated with the Expression of Cyclooxygenase-2 in Non-Small Cell Lung Cancers.: Sung Jig Lim, Hyun Jung Kim, Jung Yeon Kim, Kyeongmee Park; Korean J Pathol. 2006;40(1):17-23.

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Abstract PDF: BACKGROUND
The overexpression of Cox-2 in tumors is important for tumor invasion, angiogenesis, resistance to apoptosis and the suppression of host immunity. Moreover, a tumor's CD44 expression plays an important role in tumor invasion and metastasis. We examined the expression of COX-2 and also CD44 and its variants as well as the biological implications and relationship between Cox-2 and the CD44 variants in non-small cell lung carcinoma.
METHODS
The expressions of Cox-2 and also CD44s and its variants (CD44v3 and CD44v6) were examined by performing immunohistochemistry on 98 surgical specimens.
RESULTS
The expressions of CD44s, CD44v3 and CD44v6 were significantly more frequent in squamous cell carcinoma specimens than in the adenocarcinoma (CD44s, p=0.033; CD44v3, p=0.007; CD44v6, p=0.022). The loss of CD44s and CD44v3 were significantly correlated with poor tumor differentiation (CD44s, p=0.03; CD44v3, p=0.011). Patients with Cox-2 positive-adenocarcinoma tumors had a significantly worse cumulative survival than did those adenocarcinoma patients without the Cox-2 (p=0.048). The expression of Cox-2 was significantly associated with the CD44s expression in non-small cell lung cancer, and especially in squamous cell carcinoma.
CONCLUSIONS
These findings suggest that expression of CD44s is associated with the expression of Cox-2 in NSCLC, and especially squamous cell carcinoma.

Expressions of Cyclin E-pathway Proteins (cyclinE, cdk2, p21, p27, p57) and Their Prognostic Significance in Non-small Cell Lung Carcinomas.: Ji Han Jung, Gyeongsin Park, Myung Ah Lee, Jae Ho Byun, Chan Kwon Jung, Heejeong Lee, Kyo Young Lee, Sang In Shim, Chang Suk Kang; Korean J Pathol. 2006;40(1):24-31.

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Abstract PDF: BACKGROUND
The aberrant expression of cyclins, cdk and cdk inhibitor has been shown to be involved in oncogenic transformation. The aim of this study was to investigate the expression of the cyclin E-pathway proteins (cyclin E, cdk2, p21, p27, p57) in human non-small cell lung carcinomas (NSCLC) and also to evaluate the clinical significance of these expressions.
METHODS
A total of 203 consecutive patients with completely resected pathological stage I-III NSCLC were retrospectively reviewed. The expressions of cyclin E, cdk2, p21, p27 and, p57 was examined by performing immunohistochemistry with using the tissue microarray method.
RESULTS
In the total cases, the expression levels of cyclin E, cdk2, p21, p27 and p57 were 39.9% (81/203), 48.3% (98/203), 68.0% (138/203), 32.5% (66/203) and 2.7% (5/203), respectively. The overexpression of cyclin E and cdk2 was significantly and inversely correlated with the histologic differentiation in the adenocarcinoma (p<0.05), but not in the squamous cell carcinoma. Among the clinicopathologic factors, the stage and lymph node metastasis were associated with overall survival (p<0.05). Among these proteins, the negative expression of p21 was significantly correlated with a shortened survival rate (p<0.05).
CONCLUSIONS
These data suggest that the overexpression of cyclin E and cdk2 and the loss of p21 and p27 are associated with tumor progression in NSCLC. The aberrant expression of p21 is correlated with a poor prognosis. Therefore the immunohistochemical analysis of this protein as well as the clinical stage and, lymph node metastasis may be useful tools for evaluating the prognosis of NSCLC patients.

Expression of the GLUT1 and p53 Protein in Atypical Mucosal Lesions Obtained from Gastric Biopsy Specimens.: In Gu Do, Youn Wha Kim, Yong Koo Park; Korean J Pathol. 2006;40(1):32-38.

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Abstract PDF: BACKGROUND
The diagnosis of atypical mucosal lesions by performing hematoxylin-eosin staining is too subjective, and it is also subject to considerable inter-observer variation. There is a need for reliable immunohistochemical markers that can give reproducible results and that are not subject to individual interpretation.
METHODS
We reviewed a total of 199 cases of gastric biopsy specimens, which were all diagnosed as atypical mucosal lesions, and 124 cases of the adenocarcinomas specimens had been classified from category 1 (C1) to C5 according to the Vienna classification. We also examined the immunohistochemical expressions of the glucose transporter GLUT1 and the p53 protein in the gastric biopsy specimens to determine if they were useful markers for differentiatial diagnosis under the Vienna classifications.
RESULTS
None of the specimens in categories C1 to C3 showed GLUT1 expression, but 10.1% of the C4 specimens and 25.0% of the C5 specimens were GLUT1-positive (p<0.05). The expression of p53 was undetectable in the C1 specimens, but this was expressed in 2.9% of the C2 specimens, 15.6% of the C3 specimens, 37.8% of the C4 specimens, and 65.3% of the C5 specimens (p<0.05).
CONCLUSIONS
The Vienna classification is very applicable to the gastric biopsy specimens of the atypical mucosal lesions, and the GLUT1 and p53 expressions are candidates as highly useful markers to differentiate the Vienna C4 lesions from the C3 and C5 lesions.

Expression of Heat Shock Protein 27 and Apoptosis in Renal Cell Carcinomas.: Ghil Suk Yoon; Korean J Pathol. 2006;40(1):39-45.

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Abstract PDF: BACKGROUND
Heat shock protein 27 (HSP27) is induced by heat shock and other pathophysiologic stresses, including neoplastic transformation. We examined the relationship between the HSP27 expression and the clinical and histologic parameters to elucidate the biologic and prognostic significance of HSP27 in renal cell carcinomas (RCCs). Its regulation of apoptosis in RCC development was also observed.
METHODS
We performed immunohistochemical studies for HSP27, caspase 3 and TUNEL on paraffin-embedded tissue microarray specimens from 48 RCCs.
RESULTS
There was a tendency to higher expression of HSP27 in the RCC than in normal renal tubular cells. Of the 48 RCCs, the HSP27 expression was positive in 38 cases. An inverse relationship was found between the Fuhrman nuclear grade and HSP27 expression, but this was without statistical significance (r=-0.218, p=0.093). No relationship between the HSP27 expression and the other parameters was observed. Also, no statistically significant difference was observed between apoptosis and the HSP27 expression more (p=0.951).
CONCLUSIONS
Although HSP27 expression was increased in RCC than in normal renal tubular cell the HSP27 expression may not be a powerful and statistically significant prognostic indicator in patients with RCC.

Effects of Genistein and Daidzein on the Growth of Human Colon Cancer HCT-116 Cells.: Jong Heon Shin, Ku Seong Kang, Joung Ok Kim, Ghil Suk Yoon, Tae Gyun Kwon, Jung Wan Kim, Yoon Kyung Sohn; Korean J Pathol. 2006;40(1):46-51.

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Abstract PDF: BACKGROUND
Genistein and daidzein are two major soybean isoflavones. They have received increasing attention because of their possible roles for cancer prevention. However, their mechanisms of action and molecular targets on the human colon cancer cells are not fully understood.
METHODS
Human colon cancer HCT-116 cells were treated with genistein and daidzein to investigate their effects on the cell growth and this was analyzed with MTT assay. TUNEL assay and Hoechst33342 stain were carried out to identify apotosis.
RESULTS
Daidzein was able to inhibit cell proliferation and induce apoptosis of the HCT-116 cells, but genistein didn't affect the cell growth. The ER antagonist ICI182780 didn't attenuate the antiproliferative and proapoptotic effects of daidzein: this means the effect of daidzein on the HCT-116 cells may not be dependent on the ER pathway. The other soybean isoflavone, genistein, attenuated the effects of daidzein on the HCT-116 cells and its mechanism should be elucidated.
CONCLUSIONS
These data suggest that daidzein may act as a preventive agent on human colon cancer, and its mechanism of action doesn't involve the ER-dependent pathway.

Expression of Anaphase Promoting Complex in Surgically Resected Squamous Cell Carcinoma and Adenocarcinoma of the Lung.: Ji Sun Song, Soon Hee Jung, Minseob Eom, Sang Yeop Yi, Kwang Hwa Park, Yup Kang, Ho Young Kim; Korean J Pathol. 2006;40(1):52-59.

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Abstract PDF: BACKGROUND
The anaphase promoting complex (APC) promotes the degradation of mitotic cyclins as well as other substrates involved in sister chromatid adhesion. This study was carried out to examine the relationship between the APC expression and the clinicopathological variables, in an attempt to determine the role of the APC in the proliferation of lung cancer and to evaluate the possibility of an aberrant APC function in surgically resected squamous cell carcinomas and adenocarcinomas of the lung.
METHODS
Immunohistochemical staining was performed for APC, Ki-67, cyclin B1, Cdc2, MMP-2 and VEGF in 55 cases of squamous cell carcinoma and 34 cases of adenocarcinoma of the lung, using the avidin-biotin-peroxidase method.
RESULTS
The immunohistochemical stains for APC revealed a positive reaction in 49 cases (55.1%). The APC expression level was higher in the cyclin B1-positive group (p= 0.01), the Cdc2-positive group (p=0.001), the MMP-2-positive group (p=0.03), the group with lymph node metastasis (61.4% vs 48.9%), and the group with stage II/III cancer (60.7%) compared with those with stage I (42.9%).
CONCLUSIONS
The APC may have an aberrant function, such as a change in its role in controlling the cell cycle, and might be associated with the invasiveness and proliferation of tumor cells.

Expressions of Id-1 and Id-2 in Hyperplastic Thyroid Tissue and Thyroid Carcinoma.: Young A Kim, Young Joo Park, Do Joon Park, Seong Hoe Park, Ji Eun Kim; Korean J Pathol. 2006;40(1):60-65.

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Abstract PDF: BACKGROUND
Id proteins are a family of helix-loop-helix proteins and are regarded to be negative regulators of cell differentiation. In general, Id-1 and Id-2 expressions are upregulated during tumor development and progression in a variety of neoplasms, and these expressions may be associated with aggressive tumor behavior. However, little is known about the roles of Id-1 and Id-2 in thyroid neoplasms.
METHODS
The expressions of Id-1 and Id-2 were assessed immunohistochemically in 310 normal, hyperplastic, and neoplastic thyroid tissues using tissue microarrays.
RESULTS
Normal thyroid tissues rarely expressed Id-1 or Id-2. Moreover, whilst Id-1 expression was more elevated in malignant thyroid tissue than in hyperplastic thyroid tissue, Id-2 expression was more variable. No significant differences were observed between histologic subtypes of thyroid carcinomas with respect to Id-1 or Id-2 expression. Follicular adenomas showed higher expressions of Id-1 and Id-2 than thyroid carcinomas. No significant association was found between clinicopathological parameters and Id-1 expression, though Id-2 expression was significantly reduced in metastatic, stage IV tumors.
CONCLUSION
The expressions of Id-1 and Id-2 were elevated in hyperplastic and neoplastic thyroid tissues. However, neither appears suitable as a marker of malignancy or an aggressive phenotype, although Id-2 expression in advanced thyroid carcinomas may reflect a favorable prognosis.

Case Reports

Synchronous Invasive Ductal Carcinoma and Metastatic Ovarian Serous Papillary Adenocarcinoma in the Same Breast: A Case Report.: Hyun Jung Kim, Sung jig Lim, Sehwan Han, Ji Young Kim, Kyeongmee Park; Korean J Pathol. 2006;40(1):66-69.

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Abstract PDF: A 59-year-old woman displayed multiple palpable right breast masses along with ipsilateral cervical and axillary lymphadenopathy. She had a previous history of bilateral salpingo-oopho- rectomy for serous papillary adenocarcinoma two and half years ago. She underwent mastectomy for the lesions located in the upper inner breast quadrant. A 1 cm-sized primary ductal carcinoma was present; however, the other breast lesions and the metastatic axillary lymph nodes were confirmed as showing papillary serous adenocarcinoma, which were similar to the previous ovarian tumor. After the patient underwent postoperative adjuvant chemotherapy, of 8 cycles of doxorubicin and docetaxel, she has been stable during the clinical follow-up for 10 months with decreases in size of the metastatic nodules.

Heterotopic Mesenteric Ossification: A Case Report.: Hoon Kyu Oh, Jong Yup Bae; Korean J Pathol. 2006;40(1):70-72.

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Abstract PDF: Heterotopic mesenteric ossification is a very rare reactive lesion in the small bowel mesentery, and it is related with trauma or surgical operation. It is pathologically characterized by well formed bone trabeculae and prominent osteoblastic rimming and is clinically related to rapid and recurrent bowel obstruction symptoms. This unusual reactive process shares many clinical and pathologic features with myositis ossificans. We report here on a rare case of heterotopic mesenteric ossification in 28-year-old man who underwent a delayed small bowel resection 15 days after trauma.

Subcutaneous Bronchogenic Cyst of the Shoulder: A Case Report.: Ji Sun Song, Hwa Eun Oh, Sang Yeop Yi, Noh Hyuck Park, Ho Young Kim; Korean J Pathol. 2006;40(1):73-75.

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Abstract PDF: Bronchogenic cyst is an uncommon congenital anomaly that arises from maldevelopment of the primitive foregut, and is usually found in the lung and mediastinum. Cutaneous or subcutaneous bronchogenic cysts are rare, and occur especially in the shoulder region. We report here on a 40-year-old woman with a soft, nontender, cystic mass on the upper posterior aspect of the right acromioclavicular joint; this had been recognized about 20 years before. She underwent incision and drainage of the lesion at a local clinic about 1 year ago, but the wound was not healed. MRI showed an irregular-shaped dark signal intensity lesion that measured 2 x 1.5 cm in the subcutaneous fat layer. Microscopically, the cyst was lined by pseudostratified ciliated columnar epithelium that displayed squamous metaplasia. The cyst wall revealed frequent smooth muscle bundles, occasional seromucous glands and multifocal lymphocytic infiltration. This is the first reported case of subcutaneous bronchogenic cyst of the shoulder in a Korean adult.

Thyroid Papillary Carcinoma with Exuberant Nodular Fasciitis-like Stroma: A Case Report.: Kyung Hwa Lee, Jae Hun Chung, Jung Han Yoon, Kyung Whan Min, Chan Choi, Ji Shin Lee; Korean J Pathol. 2006;40(1):76-79.

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Abstract PDF: Thyroid papillary carcinoma (TPC) with exuberant nodular fasciitis-like stroma is one of the rare variants of TPC. To date, only 19 cases have been reported in the English medical literature. We report here on the the first Korean case of TPC that contained a prominent nodular fasciitis-like stroma. A 40-year-old female presented with a hard painless right neck mass that had been present for two months. Total thyroidectomy disclosed a solitary nodule in the mid portion of the right lobe that measured 25 x 20 mm. The tumor was well delineated, but it was not encapsulated. Microscopically, the tumor was a typical papillary carcinoma except that large areas of the tumor were occupied by a stroma composed of irregular fascicular spindle cells. The stromal component accounted for 60% of the tumor mass. The spindle cells exhibited neither atypism nor mitosis, and the tumor's extensive stromal cell proliferation resembled the appearance of nodular fasciitis of the soft tissues. Immunohistochemically, the spindle cells were positive for vimentin and alpha-smooth muscle actin, but they were negative for thyroglobulin, thyroid transcription factor-1, S-100 protein, CD34 and desmin, and this represents myofibroblastic features.

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