Journal of Pathology and Translational Medicine

Volume 42(6); December 2008

Original Articles

An Analysis of HER-2/neu, ERCC1, and GST-pi in Advanced Non-Small Cell Lung Cancer Patients Who are Treated with Platinum-based Chemotherapy.: Kyung Jin Seo, Byoung Yong Shim, Hoon Kyo Kim, Ji Han Jung, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee; Korean J Pathol. 2008;42(6):327-334.

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Abstract PDF: BACKGROUND
Platinum-based chemotherapy has shown to be an effective first-line treatment for patients with advanced stage, unresectable non-small cell lung cancer (NSCLC). We evaluated the response rate to combination chemotherapy with cisplatin and taxane, and the significance of the HER-2/neu, ERCC1, and GST-pi status as predictive markers for the tumor response. METHODS: The HER-2/neu, ERCC1, and GST-pi status were analyzed in the biopsy specimens obtained from 35 patients with advanced stage NSCLC prior to cisplatin plus either paclitaxel or docetaxel chemotherapy. RESULTS: The response rate of the tumors to combination chemotherapy was 62.9% (22/35). HER-2/neu was amplified in 51.4% (18/35) of the tumors, and this was observed exclusively in patients with progressive disease (p=0.014). ERCC1 was overexpressed in 77.2% of the specimens (27/35), and this showed a tendency to correlate with the tumor response (p=0.057). GST-pi was detected in 85.7% of the specimens (30/35). Seventy-seven percent of the patients with a negative HER-2/neu and positive ERCC1 status showed a partial response, which was in contrast to only a 25% response rate for the patients with a positive HER-2/neu and negative ERCC1 status (p=0.006). The overall survival was prolonged in the patients without HER-2/neu amplification (15 vs 8.5 months, respectively, p=0.008). On multivariate analysis, the HER-2/neu status remained the significant predictor of survival (p=0.005). CONCLUSIONS: A combination of the ERCC1, HER-2/neu status may define a subset of patients with the most favorable response to combination chemotherapy regimens for treating advanced NSCLC.

Prognosis of Gastrointestinal Stromal Tumors Arising in the Stomach and Small Intestine: A Retrospective Study of 126 Cases from a Single Institution.: Sang Hee Seok, Jun Mo Kim, Jung Min Bae, Se Won Kim, Sang Woon Kim, Sun Kyo Song, Young Kyung Bae; Korean J Pathol. 2008;42(6):335-343.

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Abstract PDF: BACKGROUND
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract. As all GISTs have the potential for aggressive clinical behavior, the guidelines for defining the risk of aggressive behavior have been developed and they have been recently revised to precisely assess these patients' prognosis.
METHODS
We analyzed 94 gastric and 32 small intestinal GISTs to compare the patients' survival with the risk stratification (original and revised). RESULTS: For gastric GISTs, 10 mitoses/50HPF was an important cutoff value for the risk of metastasis (1.3% vs 29.4%, respectively), whereas 16.7% of all the small intestinal GISTs with less than 5 mitoses/50HPF metastasized. The small intestinal GISTs showed higher frequencies of mucosal invasion and coagulation necrosis than did the gastric ones. Gastric GISTs had a significantly lower incidence of metastasis/recurrence than did the small intestinal ones in the same risk group. On multivariate analysis, the anatomic location (small intestine), the tumor size (>10 cm) and the mitotic count (>10/50HPF) were independent prognostic factors for a shorter disease-free survival for patients with GISTs. The mitotic count was more important than tumor size for both gastric and small intestinal GISTs.
CONCLUSION
Small intestinal GIST is a more aggressive tumor than gastric GIST and the mitotic count is the most important prognostic factor for GISTs.

Progressive Suppression of Selenium Binding Protein 1 in Gastric Adenoma and Adenocarcinoma.: Hyunki Kim, Hyun Ju Kang, Jong Pil Park, Ju Yeon Pyo, Hoguen Kim; Korean J Pathol. 2008;42(6):344-350.

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Abstract PDF: BACKGROUND
Human selenium binding protein 1 (SELENBP1) is a protein that binds selenium as a cofactor. The decreased expression of SELENBP1 in several types of carcinomas and its association with a poor prognosis have previously been reported on. In this study, we evaluated the expression of SELENBP1 in low-grade and high-grade epithelial dysplasia/ adenomas and adenocarcinomas. METHODS: We analyzed 45 cases of low-grade epithelial dysplasia/adenomas, 42 cases of high-grade epithelial dysplasia/adenomas and 64 cases of adenocarcinomas and all of them were obtained from endoscopic mucosal resection or endoscopic submucosal dissection. We analyzed all of them for their SELENBP1 expression by immunohistochemistry. Eight triple-paired cases of gastric mucosa, adenoma and adenocarcinoma from the same patient were selected for RT-PCR analysis. RESULTS: There was a progressive decrease in the expression of SELENBP1 from the low-grade dysplasia/adenomas (42/45, 93%) to the high-grade dysplasia/adenomas (29/42, 69%) and finally to the adenocarcinomas (24/64, 37%), (p<0.001). The progressive decrease in the SELENBP1 expression was also evident in the eight paired cases that were analyzed by RT-PCR. CONCLUSIONS: Our findings demonstrate that the SELENBP1 expression is suppressed in gastric epithelial dysplasia/adenomas and adenocarcinomas. The suppression of SELENBP1 was significantly more frequent and severer in the adenocarcinomas than that in the low-grade dysplasia/ adenomas, and this implies that the suppression of SELENBP1 is a late event in gastric carcinogenesis.

The Differential Expressions of the Epithelial-Mesenchymal Transition Regulator, Slug and the Cell Adhesion Molecule, E-cadherin in Colorectal Adenocarcinoma.: Ran Hong, Dong Yul Choi, Sung Chul Lim, Chae Hong Suh, Keun Hong Kee, Mi Ja Lee; Korean J Pathol. 2008;42(6):351-357.

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Abstract PDF: BACKGROUND
Slug is a member of the Snail family of transcription factors, and it plays a crucial role in the regulation of the epithelial-mesenchymal transition by suppression of several epithelial proteins and adhesion molecules, including E-cadherin. METHODS: The aim of the present study was to examine the significance between the expression of Slug in colorectal adenocarcinoma (CRA) specimens and the clinicopathological parameters of CRA, as determined by immunohistochemical analysis, and to determine the correlation between the Slug and E-cadherin expressions in non-neoplastic colorectal mucosa (n=45), primary CRA (n= 109) and metastatic CRA (n=17). A semiquantitative scoring system was applied based on the intensity and extent of the positive immunohistochemical staining. RESULTS: The expressions of Slug and E-cadherin were associated with the depth of tumor invasion (pT) (p=0.019, p=0.001, respectively), and these expressions showed a significant inverse correlation (p<0.001) each other. CONCLUSIONS: Our results demonstrated a positive role for Slug in the development of CRA, and Slug is a mediator of tumor invasion in CRA. In addition, an up-regulated Slug expression is significantly correlated with the loss of an E-cadherin expression, which suggests that Slug may play some role in the epithelial-mesenchymal transition (EMT) by down-regulating the E-cadherin expression.

Association of CXCR4 Expression with Metastasis and Survival among Patients with Non-small Cell Lung Cancer.: Joon Seon Song, Jin Kyung Jung, Jong Chul Park, Dong Kwan Kim, Se Jin Jang; Korean J Pathol. 2008;42(6):358-364.

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Abstract PDF: BACKGROUND
Expression of CXCR4 chemokine receptor, initially described to be involved in the homing of lymphocytes in inflammatory tissue, on breast cancer cell lines is associated with the development of lung metastases. In the present study, we evaluated CXCR4 expression in patients with non-small cell lung cancer (NSCLC). METHODS: Tissue microarray blocks were constructed from 408 formalin-fixed, paraffin-embedded NSCLC samples and analyzed via immunohistochemical staining. RESULTS: We observed CXCR4 expression in 214 (66.3%) of the 323 tumors with cytoplasmic or nuclear staining patterns. These tumors were then divided into 109 negative, 166 weak-positive and 48 strong-positive expression groups. Strong expression of CXCR4 correlated with NSCLC recurrence (p=0.047) and distant metastasis (p=0.035). However, lymph node metastasis (p=0.683) and locoregional recurrence (p=0.856) were not associated with CXCR4 expression. Interestingly, the median overall survival times relative to CXCR4 expression were 71 months in the CXCR4-negative group, 43 months in the weakly positive CXCR4 group and 23 months in the strongly positive CXCR4 group. Strongly positive CXCR4 staining was associated with significantly worse outcomes (p=0.005, log-rank test).
CONCLUSIONS
Expression of CXCR4 was associated with distant NSCLC metastases and shorter survival times.

The Expression of Galectin-3 and Galectin-7 in Epithelial Dysplasia and Adenocarcinoma of the Stomach.: Ji Eun Kwak, Han Seong Kim, Mee Joo, Sun Hee Chang, Sang Hwa Shim, Hye Ran Lee; Korean J Pathol. 2008;42(6):365-372.

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Abstract PDF: BACKGROUND
Galectin-3 and galectin-7 may play roles in human carcinogenesis. The aim of this study was to investigate the expressions of galectin-3 and galectin-7 in gastric dysplasia and adenocarcinoma. METHODS: We examined the expressions of galectin-3, galectin-7, and P53 in nonneoplastic gastric mucosa, gastric epithelial dysplasia (GED), and adenocarcinoma by immunohistochemistry. Twenty cases of nonneoplastic gastric mucosa, 20 cases of low grade GED, 20 cases of high grade GED, 40 cases of early gastric cancer (EGC), and 60 cases of advanced gastric cancer (AGC) are included for study. RESULTS: In the nonneoplastic tissue, only galectin-3 was expressed in the intestinal metaplasia. Galectin-7 was not stained in the nonneoplastic gastric mucosa. Galectin-3 was expressed in 3 cases of low grade GED (15%), 13 cases of high grade GED (65%), 2 cases of EGC (5%), and 5 cases of AGC (8%), respectively. Galectin-7 was expressed in 2 cases of low grade GED (10%), 3 cases of high grade GED (15%), and 4 cases of EGC (10%), respectively. However, it was not expressed in AGC.
CONCLUSIONS
Based on our results, the expressions of galectin-3 and galectin-7 may contribute to the development of gastric epithelial dysplasia and early gastric cancer, rather than contributing to the progression of gastric adenocarcinoma.

Histological and Immunohistochemical Evaluation of Ductal Carcinoma In Situ Co-Existing with Triple-Negative Carcinoma of the Breast.: Hyesil Seol, Hyoungsuk Ko, In Ae Park; Korean J Pathol. 2008;42(6):373-380.

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Abstract PDF: BACKGROUND
Triple-negative breast carcinomas (TNBCs) are associated with high-grade histological tumor and a poor clinical outcome. In this study, we evaluated the histology and immunohistochemical features of DCIS co-existing with TNBC to determine the characteristics of the precursor lesions of TNBC. METHODS: Among the 1,610 cases of breast carcinoma, we selected the TNBCs with DCIS (n=196), and compared the pathological and immunohistochemical findings of the DCIS with those of the invasive carcinoma areas.
RESULTS
Among the 1,610 breast carcinomas, the TNBCs accounted for 330 cases (20.5%) and there were 196 cases with DCIS. The TN-DCIS cases exhibited high nuclear (94.5%) and histological (94.5%) grades, comedo-necrosis (68.9%) and a small extent of the DCIS-involved area. Immunohistochemically, a p53 expression was present in 48.4% of the TN-DCIS cases and a high Ki-67 index was present in 31.5%. The same TN immunohistochemical profiles as the carcinoma were detected in 109 of the 124 (87.9%) cases, but different profiles were observed in 15 of the 124 (12.1%) cases. The 15 discordant cases were associated with a low histological grade (p=0.037), low p53-positivity (p=0.006) and a low Ki-67 index (p=0.026), as compared to the invasive carcinomas. CONCLUSIONS: The results of this study suggest that TN DCIS is a highly probable, but not obligate, precursor lesion of TNBC.

The Prognostic Significance of Neuroendocrine Differentiation for Treating Prostatic Carcinoma in 699 Cases of Radical Prostatectomy.: Tae Hoon Kang, Eun Shin, Baek Hee Kim, Gheeyoung Choe; Korean J Pathol. 2008;42(6):381-388.

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Abstract PDF: BACKGROUND
Neuroendocrine differentiation of prostatic carcinoma is known to be associated with a poor prognosis, tumor progression and androgen-independency, and there is currently no successful therapy for this type of tumor. The purpose of this study is to evaluate the prognostic implications of neuroendocrine differentiation in prostatic carcinoma in Korean men. METHODS: Six hundreds and ninety nine consecutive cases of radical prostatectomy specimens were systematically processed for topographic mapping. Neuroendocrine differentiation was detected by immunohistochemistry by using antibody to chromogranin. We analyzed the relationship between neuroendocrine differentiation and the clinicopathological prognostic factors, as well as biochemical failure. The neuroendocrine differentiation was evaluated according to the presence of chromogranin-positive cells, the pattern of neuroendocrine cells and the number of neuroendocrine cells, respectively.
RESULTS
Neuroendocrine differentiation was detected in 150 out of 699 cases (21.5%). The presence of neuroendocrine differentiation as well as the pattern of neuroendocrine cells was correlated with biochemical failure and the other clinicopathological prognostic factors such as the Gleason score, the pathologic stage, the tumor volume, angiolymphatic invasion, perineural invasion, and the Ki-67 proliferative index (p<0.05). CONCLUSIONS: We suggest that neuroendocrine differentiation of prostatic carcinoma is a prognostic factor even in radical prostatectomy specimens for localized prostate cancer. Evaluation of the presence of neuroendocrine differentiation as well as the pattern of neuroendocrine cells is recommended in radical prostatectomy specimens.

Case Reports

Uterine Cervical Large Cell Neuroendocrine Carcinoma Concurrent with High Grade Squamous Intraepithelial Neoplasia: A Case Report.: Yun Kyung Kang, Jae Whoan Koh; Korean J Pathol. 2008;42(6):389-392.

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Abstract PDF: Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare and aggressive malignancy. We report a case of uterine cervical LCNEC concurrent with high grade squamous intraepithelial neoplasia (HG-SIN). The LCNEC expressed chromogranin A and thyroid transcription factor 1 (TTF1). The HG-SIN was negative for these markers. Human papillomavirus (HPV) type 18 was positive in LCNEC whereas both type 16 and 18 were positive in HG-SIN by nested polymerase chain reaction. This case showed TTF1 positivity nonetheless diagnosed as a primary uterine cervical LCNEC confirmed by the detection of HPV genome within the tumor. It is critical to recognize LCNEC of the uterine cervix even in the small biopsy specimen because it is a distinctive clinicopathological entity with highly aggressive behavior and unfavorable outcome.

Solitary Pulmonary Mixed Squamous Cell and Glandular Papilloma: A Brief Case Report.: Chan Ohk Sung, Jhingook Kim, In Gu Do, Joungho Han; Korean J Pathol. 2008;42(6):393-395.

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Abstract: Pulmonary mixed squamous cell and glandular papillomas are extremely rare-only a few cases have been reported worldwide. We report a case of mixed squamous cell and glandular papilloma that presented as a solitary pulmonary nodule in a 53-year-old man. The tumor was located in the peripheral small bronchus of the posterobasal segment of the right lower lobe. Microscopically, the tumor was composed of papillary structures lined by squamous and glandular epithelium with mucous material. The fibrovascular cores showed lymphoplasmacytic infiltrates.

Adenocarcinoma Arising in Type 1 Congenital Cystic Adenomatoid Malformation: A Case Report and Review of the Literature.: Jinyoung Yoo, Sun Mi Lee, Ji Han Jung, Myeong Im Ahn, Deog Gon Cho, Seok Jin Kang, Kyo Young Lee; Korean J Pathol. 2008;42(6):396-400.

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Abstract PDF: Malignancies in congenital cystic adenomatoid malformations (CCAMs) of the lung are rare. We report a 41-year-old male patient with a pulmonary cystic lesion suspicious for CCAM, unrecognized until the patient was 40 years of age, and which subsequently became more consolidated during the interval between initial presentation and surgery. Microscopic examination of the resected specimen revealed features of type 1 CCAM with a mucinous adenocarcinoma, metastatic to the mediastinal lymph nodes. This case illustrates the importance of prompt surgical resection for all suspected CCAMs, especially those discovered in adulthood.

Paraganglioma of the Thyroid: A Case Report.: Jin Joo Baek, Youn Soo Lee, Chang Seok Kang, Sang In Sim, Kyo Young Lee; Korean J Pathol. 2008;42(6):401-404.

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Abstract PDF: Paragangliomas (PGs) of the thyroid are very rare tumors. Based on the medical literature, thyroid PGs invariably affected women and they were always thought to be benign, and they have always been mistaken for other more common lesions. We report here on the first case of PG of the thyroid in a 45-year-old man in Korea. Ultrasonographically, the tumor showed hypoechoic features. Microscopically, the tumor showed the typical zellballen pattern. The small to medium-sized tumor cells contained moderate amounts of finely granular eosinophilic cytoplasm and round to oval nuclei with fine chromatin. The tumor invaded the thyroid capsule and the extrathyroidal tissue with vascular and perineural invasion. Immunohistochemically, the tumor showed positivity for chromogranin, S-100 protein, CD56a, and synaptophysin and negativity for calcitonin, thyroglobulin, galectin-3, p53, CK19, and EMA. The Ki-67 labeling Index was 10%. We concluded that our case has a high potential of metastasis, and a close follow up would be important.

Pancreatic Pseudocyst with Splenic Involvement: A Case Report.: Jeong Hwan Chun, Han Seong Kim, Mee Joo, Sun Hee Chang, Ji Eun Kwak, Sang Hwa Shim, Chul Nam Kim, Soon Joo Cha; Korean J Pathol. 2008;42(6):405-408.

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Abstract PDF: There have been a few reported cases of pancreatic pseudocyst with involvement of adjacent structures including the stomach, duodenum, and even the mediastinum. An intrasplenic pancreatic pseudocyst is an uncommon complication of acute or chronic pancreatitis. We report a case of pancreatic pseudocyst with splenic involvement in a 69-year-old man with a review of literatures. Abdominal CT revealed a 4 cm sized cyst at the pancreatic tail which was extending into the splenic hilum and splenic parenchyma. Distal pancreatectomy and splenectomy was performed. Pathologic findings demonstrated a pseudocyst of pancreatic tail which communicated with the infacted splenic parenchyma. Also vasculitis, endothelial hyperplasia and medial calcification of the splenic artery were observed.

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