Journal of Pathology and Translational Medicine

Volume 42(2); April 2008

Original Articles

The Expression of G1-S Cell Cycle Inhibitors in Normal Placenta and Gestational Trophoblastic Diseases.: Yan Hua Xuan, Kyung Hee Kim, Yoon La Choi, Geung hwan Ahn, Seoung Wan Chae, Ho chang Lee, Ok Jun Lee, Seok Hyung Kim; Korean J Pathol. 2008;42(2):67-74.

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Abstract PDF: BACKGROUND
The objective of this study is to determine the expression pattern of G1-S inhibitor molecules in normal trophoblasts and gestational trophoblastic diseases, including hydatidiform moles and choriocarcinoma.
METHODS
A total of 157 cases comprising 47 normal placentas and 110 gestational trophoblastic diseases such as choriocarcinoma (19 cases) and hydatidiform moles (91 cases of which 58 were complete, 12 were partial and 21 were invasive mole) were immunohistochemically analyzed on paraffin blocks using anti-p21, antip27, anti-p16, anti-p53, anti-pRb antibodies.
RESULTS
The results revealed that in the normal placenta, all the G1-S cell cycle inhibitors were maximally expressed by the first-trimester trophoblasts and these levels decreased with gestational age. The expression of p21 and p53 was greatly enhanced in the gestational trophoblastic diseases, particularly in invasive mole and choriocarcinoma, whereas the p27 expression was significantly downregulated in choriocarcinoma. Especially, Rb expression was typically enhanced in the invasive mole, but not in choriocarcinoma. The expression level of p16 was low in all the cases, and particularly in choriocarcinoma.
CONCLUSIONS
In conclusion, we demonstrated that the expression of G1/S cell cycle inhibitors correlates well with normal trophoblast differentiation, and these expressions are considerably altered in the gestational trophoblastic diseases, including complete/partial/ invasive hydatidiform mole and choriocarcinoma.

Correlation Between Cyclooxygenase-2 Expression and HuR Cytoplasmic Translocation of Breast Cancer.: Sung Im Do, In Gu Do, Gou Young Kim, Sun Lee, Youn Wha Kim, Yong Koo Park, Juhie Lee, Sung Jig Lim; Korean J Pathol. 2008;42(2):75-80.

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Abstract PDF: BACKGROUND
Embryonic lethal abnormal vision (ELAV)-like protein HuR is known to stabilize mRNA through binding AU-rich elements in the 3'-untranslated region. Recent studies show that HuR expression is associated with the expression of several genes including cyclooxygenase-2 (COX-2). HuR exists predominantly in the nucleus, but cytoplasmic translocation of HuR is thought to be more important for its activity. COX-2 is a well-known enzyme that promotes tumor growth.
METHODS
To evaluate the correlation of HuR and COX-2 expression, we analyzed expression of HuR and COX-2 in 91 cases of breast cancer using immunohistochemistry.
RESULTS
Nuclear and cytoplasmic expression of HuR was seen in 76 (83.5%) and 19 (20.9%) of 91 cases respectively. COX-2 immunoreactivity was seen in 54 (59.4%) cases. Cytoplasmic HuR expression showed significant correlation with COX-2 expression (p=0.001). Nuclear HuR showed no correlation with COX-2 expression or other clinicopathological parameters. COX-2 expression is significantly associated with tumor grade (p=0.028). COX-2 (p=0.092) and cytoplasmic (p=0.569) and nuclear HuR (p=0.247) expression showed no correlation with survival.
CONCLUSIONS
These results suggest that cytoplasmic HuR expression is associated with COX-2 expression in breast cancer and cytoplasmic location of HuR might contribute to the stabilization of COX-2 mRNA.

Immunohistochemical Markers for Metastasis in Clear Cell Renal Cell Carcinoma.: Kyungeun Kim, Cheryn Song, Jae Y Ro, Hanjong Ahn, Yong Mee Cho; Korean J Pathol. 2008;42(2):81-86.

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Abstract PDF: BACKGROUND
Renal cell carcinoma (RCC) is notorious for its high metastatic potential, and 30% of RCC patients present with metastatic disease at the initial presentation and 50% of them will develop metastasis or recurrence after radical surgery.
METHODS
In an attempt to identify the best predictive marker(s) for metastasis in patients with clear cell RCCs (CRCCs), we examined the expression patterns of 7 metastasis/prognosis-related markers by constructing a tissue microarray including primary CRCC specimens from 30 metastatic and 60 nonmetastatic CRCCs. The markers we studied were Ki-67, MUC1, CD44s, PTEN, gelsolin, CA9 and p53.
RESULTS
The expressions of Ki-67, PTEN, CD44s, gelsolin and p53 were increased, whereas those of MUC1 and CA9 were decreased in the metastatic CRCCs compared with the non-metastatic CRCCs. The receiver operating characteristic curve-area under the curve (AUC) value of Ki-67 was 0.671, which was the highest among the 7 markers. The optimal cut-off value, sensitivity and specificity of the Ki-67 expression were 1.67%, 86.7% and 41.7%, respectively.
CONCLUSIONS
These results demonstrate that the Ki-67 expression was increased in metastatic CRCCs, and it had the highest predictive value among the 7 markers. This suggests that Ki-67 could be an excellent predictive marker for metastasis in CRCC patients.

A Multiinstitutional Consensus Study on the Pathologic Diagnosis of Endometrial Hyperplasia and Carcinoma.: Kwang Sun Suh, Insun Kim, Moon Hyang Park, Geung Hwan Ahn, Jin Hee Sohn, In Ae Park, Hye Kyoung Yoon, Kyu Rae Kim, Hee Jung An, Dong Won Kim, Mi Jin Kim, Hee Jae Joo, Eun Kyung Kim, Young Hee Choi, Chong Woo Yoo, Kyung Un Choi, Sang Yeop Yi, Hye Sun Kim, Sung Ran Hong, Hee Jeong Lee, Sun Lee; Korean J Pathol. 2008;42(2):87-93.

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Abstract PDF: BACKGROUND
The purpose of this study was to examine the reproducibility of both the diagnosis of endometrial hyperplasia (EH) or adenocarcinoma, and the histologic grading (HG) of endometrioid adenocarcinoma (EC).
METHODS
Ninety-three cases of EH or adenocarcinomas were reviewed independently by 21 pathologists of the Gynecologic Pathology Study Group. A consensus diagnosis was defined as agreement among more than two thirds of the 21 pathologists.
RESULTS
There was no agreement on the diagnosis in 13 cases (14.0%). According to the consensus review, six of the 11 EH cases (54.5%) were diagnosed as EH, 48 of the 57 EC cases (84.2%) were EC, and 5 of the 6 serous carcinomas (SC) (83.3%) were SC. There was no consensus for the 6 atypical EH (AEH) cases. On the HG of EC, there was no agreement in 2 cases (3.5%). According to the consensus review, 30 of the 33 G1 cases (90.9%) were G1, 11 of the 18 G2 cases (61.1%) were G2, and 4 of the 4 G3 cases (100.0%) were G3.
CONCLUSIONS
The consensus study showed high agreement for both EC and SC, but there was no consensus for AEH. The reproducibility for the HG of G2 was poor. We suggest that simplification of the classification of EH and a two-tiered grading system for EC will be necessary.

Epidermal Growth Factor Receptor Expression of Non-small Cell Carcinoma and Its Relationship with Genomic Mutation.: Sang hee Seok, Mi Jin Kim; Korean J Pathol. 2008;42(2):94-99.

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Abstract PDF: BACKGROUND
It has recently been clarified that epidermal growth factor receptor (EGFR), which is a receptor tyrosine kinase of the erbB family, is abnormally activated in non-small cell lung carcinomas (NSCLC) and this fact is being utilized for creating targeted therapy. In this study, we aimed to identify the frequency of the EGFR expression and gene mutation in NSCLC, and to determine the correlation between them.
METHODS
Immunohistochemical staining for EGFR, C-erbB-2, cytokeratin 7, p53 and thyroid transcription factor-1, and EGFR mutation analysis were performed using paraffin-embedded archival tissue from 228 cases of NSCLC; this included 112 squamous cell carcinomas and 116 adenocarcinomas.
RESULTS
An EGFR expression and gene mutation occurred in 112 casees (53.5%) and 52 cases (22.8%), respectively. EGRF mutation was more frequent in the adenocarcinomas than in the squamous cell carcinomas, in non-smokers than in smokers, and in females than in males. EGFR mutation was significantly associated with an EGFR protein expression, and especially in adenocarcinomas.
CONCLUSION
The EGFR expression in NSCLC was associated with EGFR mutation, and especially in adenocarcinomas. More studies are needed to prove the clinical significance of the EGFR expression for creating targeted therapy to treat NSCLC.

Case Reports

Secondary Oxalosis Involving the Epididymis.: Sangkyum Kim, Kwanggi Lee, Namhoon Cho; Korean J Pathol. 2008;42(2):100-102.

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Abstract PDF: Secondary oxalosis in the epididymis is a rare complication among patients who have undergone hemodialysis or peritoneal dialysis. This case report presents secondary oxalosis confirmed via a clinicoradiological-pathologic process-in combination with clinical symptoms, ultrasonographic findings, cytologic findings in urine, and surgical pathological diagnosis.

Diffuse Embryoma of the Testis: A Case Report.: Won Ae Lee; Korean J Pathol. 2008;42(2):103-107.

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Abstract PDF: Diffuse embryoma of the testis is a very rare, distinct form of mixed germ cell tumor. I report here on a case of diffuse embryoma in a 22-year-old male who presented with painful scrotal swelling. The resected testis was entirely occupied by a non-encapsulated tumor mass. The cut surface of the tumor was grey or whitish pink, soft and granular with foci of hemorrhage and necrosis. Microscopically, the tumor was characterized by a diffuse, orderly arrangement of embryonal carcinoma and yolk sac tumor in almost equal proportions. The yolk sac tumor component was diffusely wrapped around the embryonal carcinoma. Syncytiotrophoblasts were scattered throughout the tumor. Minor foci of immature teratoma, seminoma and intratubular germ cell neoplasia were observed. The yolk sac tumor (YST) component was emphasized by immunoreactivity for alpha fetoprotein, whereas the embryonal carcinoma was reactive for CD30. The strong reactivity for cytokeratin in the YST component formed an outstanding contrast to the weak cytokeratin reactivity in the embryonal carcinoma.

Sarcoidosis Associated with Adenocarcinoma of the Lung: A Case Report.: Joon Seon Song, Seungkoo Lee, Yong Hee Kim, Se Jin Jang; Korean J Pathol. 2008;42(2):108-112.

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Abstract PDF: Sarcoidosis and malignant neoplasm are frequently encountered pulmonary diseases, but their combined existence in the same patient is rare. As sarcoidosis usually presents as mediastinal lymphadenopathy, its concurrence in lung cancer patient radiologically mimics mediastinal metastasis and this can be possibly interpreted as unresectable disease. We report here on a case of lung adenocarcinoma associated with sarcoidosis that developed in a 64 year-old male who underwent surgical resection. Radiological examinations revealed 5.7 cm-sized mass in the right upper lobe with an enlargement of the bilateral supraclavicular, highest mediastinal, subcarinal and the upper and lower paratracheal lymph nodes. Histologic examination showed a well differentiated adenocarcinoma with non-caseating epithelioid granulomas in the lung. The enlarged peribronchial and mediastinal lymph nodes also revealed sarcoid granulomas without cancer metastasis. A good prognosis may be expected for those cases of lung cancers with non-caseating granulomas in the regional lymph nodes. The patient presently has no symptoms or signs of tumor, without further treatment since his surgery.

A Positive Hybrid (HMW-CK and E-Cadherin) Carcinoma in situ Arising in a Phyllodes Tumor of the Breast: A Case Report.: Yun Kyung Kang, Young Hyeh Ko; Korean J Pathol. 2008;42(2):113-117.

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Abstract PDF: Malignant transformation in phyllodes tumor (PT) is uncommon and almost always confined to the stromal component. Epithelial changes like hyperplasia, metaplasia, and varying degrees of atypia are not uncommon in PT, whereas carcinomatous change is extremely rare. We report a 37-year-old woman with carcinoma in situ (CIS) arising in a benign PT. Grossly, it was a well circumscribed, 4.5 cm-sized mass. The CIS component was confined to the PT and showed overlapping ductal and lobular features with coexpression of E-cadherin and high molecular weight cytokeratin (HMW-CK). The present case emphasizes that careful investigation of multiple microscopic sections is mandatory to find a small carcinomatous lesion within PT. Expression of E-cadherin and HWM-CK in this hybrid CIS suggests that intraepithelial neoplasia of the breast arising in PT may be derived from a common progenitor of the terminal duct-lobular unit.

Chronic Sclerosing Dacryoadenitis: Report of 2 Cases.: Ji Eun Kwon, Sang Kyum Kim, Sang Ryul Lee, Woo Ick Yang, Haeryoung Kim; Korean J Pathol. 2008;42(2):118-122.

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Abstract PDF: Chronic sclerosing dacryoadenitis is a rare and under-recognized chronic inflammatory disease of the lacrimal gland. We describe 2 patients with a localized type of chronic sclerosing dacryoadenitis. Both patients presented with a slowly growing painless mass of the eyelid mimicking a tumorous lesion. The morphologic findings of the masses excised under the clinical diagnosis of lymphoma closely recapitulate those of chronic sclerosing sialadenitis (Kuttner tumor). Immunohistochemical staining demonstrated an increased population of IgG4-positive plasma cells confirming that this disease also belongs to the spectrum of a recently described IgG4-related sclerosing disease.

Adenomyoma of Endocervical Type in a First-Trimester Gravid Uterine Corpus: A Brief Report.: Hyunchul Kim, Hoiseon Jeong, Sangho Lee, Young Seok Lee, Bong Kyung Shin, Insun Kim; Korean J Pathol. 2008;42(2):123-124.

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Abstract PDF: Uterine adenomyoma is a neoplasm that is composed of endometrial glands and smooth muscle, and this is found in the uterine corpus; however, the glandular component is occasionally of mucin-secreting endocervical type. We describe here a case of uterine adenomyoma of the endocervical type, and this presented in a 38-year-old pregnant woman.

Solitary Pulmonary Lymphangioma in an Adult: A Brief Case Report.: Hye Jong Song, Joungho Han, Kwhanmien Kim, Kyung Soo Lee, Jinwon Seo; Korean J Pathol. 2008;42(2):125-127.

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Abstract PDF: Solitary pulmonary lymphangiomas are extremely rare. We report here on an unique case of solitary pulmonary lymphangioma in an adult. A well-circumscribed, 6 cm-sized, pleural based lesion with fluid attenuation was found in a 50-year-old Korean male. He had no previous history of disease or trauma. The wedge-resected lung revealed an ill-demarcated lesion with multiple microscopic cysts and the cystic walls had loose intervening stroma.

Ectopic Liver Associated with the Gallbladder: A Brief Case Report.: Hee Eun Kyeong, Younghee Park, Sanghui Park; Korean J Pathol. 2008;42(2):128-130.

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Abstract PDF: Ectopic liver is a rare entity that has been previously identified during abdominal exploration for other surgery and this has usually been described in the vicinity of the liver such as on the gallbladder, hepatic ligaments, diaphragm, thoracic cavity, adrenal glands, pancreas, omentum, spleen, esophagus and umbilical cord. Most cases of ectopic liver reported in the literature were located in the gallbladder. We report here on a case of ectopic liver related to the gallbladder, and this was encountered during an elective laparoscopic cholecystectomy.

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