Purpose: Granular corneal dystrophy type 2 (GCD2) is a hereditary disease that features granular and lattice stromal deposits in the cornea. There are homozygotes and heterozygotes and the opacities are exacerbated by corneal trauma or surgery, such as laser in situ keratomileusis (LASIK). As there is individual variability in GCD2 phenotypes, we investigated various corneal features of GCD2 patients in their twenties, the main age group for refractive surgery. Methods: From genetically confirmed GCD2 patients who had an R124H mutation of the transforming growth factor β induced (TGFBI) gene at age 20 to 29 years, we chose representative patients: one homozygote; one compound heterozygote; one simple heterozygote with a severe phenotype with many granular deposits; one common heterozygote; and four heterozygotes with normal corneas. The corneas of all patients were subject to slit-lamp examination and photographed. Results: The homozygote had confluent granular deposits covering the cornea. The compound heterozygote had granular and lattice deposits covering the center of the cornea. The patient with a severe phenotype had more than 30 granular deposits in one eye, but was a simple GCD2 heterozygote, verified by full-sequencing of the TGFBI gene. In the four patients with normal corneas, a single small lesion was subsequently detected during follow-up in two, at 3 weeks and 6 months, respectively. Both corneas were judged clear at chance examinations. Conclusions Among Koreans in their twenties, GCD2 patients have various phenotypes, from clear corneas to severe confluent opacities. There are GCD2 heterozygotes with nearly clear corneas, so caution must be taken when choosing patients for refractive surgery.

Purpose: Contrast sensitivity, the ability to distinguish the relative difference in luminance of an object from its surrounding or adjacent objects, is a useful measure of visual function. In granular corneal dystrophy type 2 (GCD2), opacity of the corneal stroma causes deterioration in visual function. We compared the contrast sensitivity of GCD2 patients before and after phototherapeutic keratectomy (PTK) to evaluate the perioperative visual function in these patients. Methods: This study included 22 eyes of heterozygote GCD2 patients. The visual acuity and contrast sensitivity were measured before and after PTK. The contrast sensitivity was measured in mesopic and photopic background luminances, with glare (G) levels of 0-2 (G0, G1, and G2, respectively) and spatial frequencies at 1.5, 3, 6, 12, and 18 cycles per degree (cpd). Results: The contrast sensitivity increased after PTK at 1.5 and 3 cpd in mesopic and photopic conditions with G0-2 glare (p < 0.05). At 6 cpd, the contrast sensitivity increased in the mesopic condition with G1 glare, and in the photopic condition with G0-2 glare (p < 0.05). However, there was no change in contrast sensitivity at any glare level at 12 and 18 cpd after PTK. Conclusions In GCD2 patients, the contrast sensitivity increased significantly after PTK. The vision of GCD2 patients, which is decreased due to corneal opacity, is improved after PTK.

BACKGROUND: Due to advancements in treatment of metastatic and advanced renal cell carcinoma (RCC), it has become increasingly important to diagnose metastatic RCC and the specific subtype. In this study, we investigated the diverse histologic features of metastatic clear cell renal cell carcinoma (CCRCC) cases in comparison with corresponding primary lesions. METHODS: We identified 119 metastatic CCRCC cases from 81 corresponding primary lesions diagnosed between 1995 and 2010 and evaluated the diverse histologic and immunohistochemical features of these lesions. RESULTS: A total of 44 primary lesions (54.3%) had a non-clear cell component in addition to a typical clear cell component. Of the 119 metastatic lesions, 63 lesions (52.9%) contained a non-clear cell component, and 29 metastatic lesions were composed of a non-clear cell component only. Rhabdoid features were the most frequent non-clear cell histology among the metastatic lesions. Metastatic CCRCCs mainly showed positive CD10 and epithelial membrane antigen staining and negative cytokeratin 7 staining. CONCLUSIONS: Metastatic CCRCC commonly showed a variety of histologic features. If there is a difficulty to diagnose metastatic CCRCC due to a variety of histologic features or small biopsy specimen, histologic review of the primary lesion and immunohistochemical analysis can help determine the correct diagnosis.
Biopsy ; Carcinoma, Renal Cell* ; Cellular Structures ; Immunohistochemistry ; Keratin-7 ; Mucin-1 ; Neoplasm Metastasis

PURPOSE: To observe long-term clinical outcomes for patients with early-stage breast cancer treated with forward intensity-modulated radiation therapy (IMRT), including local control and clinical toxicities. MATERIALS AND METHODS: We retrospectively analyzed a total of 214 patients with stage I-II breast cancer who were treated with breast conserving surgery followed by adjuvant breast radiation therapy between 2001 and 2008. All patients were treated using forward IMRT. The whole breast was irradiated to a dose of 50 to 50.4 Gy followed by an 8 to 12 Gy electron boost to the surgical bed. RESULTS: The median age was 46 years (range, 21 to 82 years) and the medial follow-up time was 7.3 years (range, 2.4 to 11.7 years). Stage T1 was 139 (65%) and T2 was 75 (35%), respectively. Ipsilateral breast recurrence was observed in 3 patients. The 5- and 10-year local control rates were 99.1% and 97.8%, respectively. The cosmetic outcome was evaluated according to the Harvard scale and 89.4% of patients were scored as excellent or good. CONCLUSION: The whole breast radiation therapy as an adjuvant treatment using a forward IMRT technique showed excellent long-term local control as well as favorable outcomes of toxicity and cosmesis.
Breast Neoplasms* ; Breast* ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Recurrence ; Retrospective Studies

BACKGROUND: Recently, there have been a few reports of renal cell carcinoma (RCC) cases with anaplastic lymphoma kinase (ALK) gene fusion. In this study, we screened consecutively resected RCCs from a single institution for ALK protein expression by immunohistochemistry, and then we performed fluorescence in situ hybridization to confirm the ALK gene alteration in ALK immunohistochemistry-positive cases. METHODS: We screened 829 RCCs by ALK immunohistochemistry, and performed fluorescence in situ hybridization analysis using ALK dual-color break-apart rearrangement probe. Histological review and additional immunohistochemistry analyses were done in positive cases. RESULTS: One ALK-positive case was found. Initial diagnosis of this case was papillary RCC type 2. This comprises 0.12% of all RCCs (1/829) and 1.9% of papillary RCCs (1/53). This patient was a 44-year-old male with RCC found during routine health check-up. He was alive without evidence of disease 12 years after surgery. The tumor showed a papillary and tubular pattern, and showed positivity for CD10 (focal), epithelial membrane antigen, cytokeratin 7, pan-cytokeratin, PAX-2, and vimentin. CONCLUSIONS: We found the first RCC case with ALK gene rearrangement in Korean patients by ALK immunohistochemistry among 829 RCCs. This case showed similar histological and immunohistochemical features to those of previous adult cases with ALK rearrangement, and showed relatively good prognosis.
Adult ; Carcinoma, Renal Cell* ; Fluorescence ; Gene Fusion ; Gene Rearrangement ; Humans ; Immunohistochemistry ; In Situ Hybridization ; In Situ Hybridization, Fluorescence ; Keratin-7 ; Lymphoma ; Male ; Mucin-1 ; Phosphotransferases ; Prognosis ; Receptor Protein-Tyrosine Kinases

BACKGROUND: Transmembrane protease serine 2-ETS related gene (TMPRSS2-ERG) gene fusion, the most common genetic alternation in prostate cancer, is associated with protein expression of the oncogene ERG. Recently, an immunohistochemical staining method using an anti-ERG antibody was shown to have a strong correlation with altered ERG protein expression. METHODS: We analyzed a total of 303 radical prostatectomy specimens (obtained from Korean prostate cancer cases) using a constructed tissue microarray and ERG immunohistochemical staining. Thereafter, we evaluated the association between ERG expression and clinicopathological factors. RESULTS: The ERG-positive rate was 24.4% (74/303) and significantly higher ERG expression was observed in the subgroup with a lower Gleason score (p=0.004). Analysis of the histologic pattern of prostate adenocarcinomas revealed that tumors with discrete glandular units (Gleason pattern 3) displayed higher frequency of ERG expression (p=0.016). The ERG-positive rate was lower than that found (approximately 50%) in studies involving western populations. Other factors including age, tumor volume, initial protein-specific antigen level, a pathological stage and margin status were not significantly related with the ERG expression. CONCLUSIONS: ERG immunohistochemical staining is significantly higher in tumors with well-formed glands and is associated with a lower Gleason score.
Adenocarcinoma ; Gene Fusion ; Humans ; Immunohistochemistry ; Neoplasm Grading ; Oncogenes ; Prostate ; Prostatectomy ; Prostatic Neoplasms ; Serine ; Tumor Burden

BACKGROUND: The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines. METHODS: Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines. RESULTS: Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity. CONCLUSIONS: This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.
Humans ; Risk Factors

BACKGROUND: The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines. METHODS: Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines. RESULTS: Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity. CONCLUSIONS: This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.
Humans ; Risk Factors

BACKGROUND: Clear cell papillary renal cell carcinoma (CCPRCC) is a recently established subtype of renal epithelial tumor. The aim of this study was to identify the diagnostic criteria of CCPRCC with an emphasis on immunohistochemical studies, and to report three cases with concurrent other-type renal cell carcinoma (RCC). METHODS: A total of 515 RCC patients that consecutively underwent surgical resection at Seoul National University Hospital from 1 January 2010 to 31 December 2011 were screened. Each case was reviewed based on the histologic features and was evaluated immunohistochemically. RESULTS: A total of 15 CCPRCCs were identified, which composed 2.9% of the total RCCs. The mean age was 52 years, and the average tumor size was 1.65 cm. All 15 cases showed low nuclear grade, no lymph node metastasis and no distant metastasis. The CCPRCCs showed variable architectural patterns including cystic, trabecular, papillary, and acinar. All of the cases showed moderate to intense immunoreactivity for cytokeratin 7 (CK7). CD10 was negative or showed focal weak positivity. Three cases had concurrent other-type RCC, including a clear cell RCC and an acquired cystic disease-associated RCC. CONCLUSIONS: The strong CK7 and negative or focal weak CD10 expression will be useful for the diagnosis of CCPRCC.
Carcinoma, Renal Cell ; Humans ; Keratin-7 ; Lymph Nodes ; Neoplasm Metastasis ; Neprilysin

PURPOSE: To investigate the care patterns for radiation therapy and to determine inter-hospital differences for patients with laryngeal carcinoma in Korea. MATERIALS AND METHODS: A total of 237 cases of laryngeal carcinoma (glottis, 144; supraglottis, 93) assembled from 23 hospitals, who underwent irradiation in the year of 1998 and 1999, were retrospectively analyzed to investigate inter-hospital differences with respect to radiotherapy treatment. We grouped the 23 hospitals based on the number of new patients annually irradiated in 1998; and designated them as group A (> or =900 patients), group B (> or =400 patients and <900 patients), and group C (<400 patients). RESULTS: The median age of the 237 patients was 62 years (range, 25 to 88 years), of which 216 were male and 21 were female. The clinical stages were distributed as follows: for glottis cancer, I; 61.8%, II; 21.5%, III; 4.2%, IVa; 11.1%, IVb; 1.4%, and in supraglottic cancer, I; 4.3%, II; 19.4%, III; 28.0%, IVa; 43.0%, IVb; 5.4%, respectively. Some differences were observed among the 3 groups with respect to the dose calculation method, radiation energy, field arrangement, and use of an immobilization device. No significant difference among 3 hospital groups was observed with respect to treatment modality, irradiation volume, and median total dose delivered to the primary site. CONCLUSION: This study revealed that radiotherapy process and patterns of care are relatively uniform in laryngeal cancer patients in Korean hospitals, and we hope this nationwide data can be used as a basis for the standardization of radiotherapy for the treatment of laryngeal cancer.
Female ; Glottis ; Humans ; Immobilization ; Korea ; Laryngeal Neoplasms ; Male ; Retrospective Studies