Hormone Receptor Expression in Invasive Breast Cancer Among Korean Women and Comparison of 3 Antiestrogen Receptor Antibodies: A Multi-institutional Retrospective Study Using Tissue Microarrays

Bae, Young Kyung,Gong, Gyungyub,Kang, Jun,Lee, Ahwon,Cho, Eun Yoon,Lee, Ji Shin,Suh, Kwang-Sun,Lee, Dong Wha Lippincott Williams Wilkins, Inc. 2012 The American journal of surgical pathology Vol.36 No.12

Estrogen receptor (ER) and progesterone receptor (PR) are prognostic markers of breast cancer and predictive markers of response to endocrine therapy. To determine rates of ER and PR expression in invasive breast carcinoma among Korean women, the Breast Pathology Study Group of the Korean Society of Pathologists collected 1198 specimens of invasive breast carcinoma from 6 university hospitals. Immunohistochemical analysis was carried out using 1 antibody against PR and 3 antibodies against ER (1D5, 6F11, and SP1). Specimens were evaluated using the semiquantitative Allred score (scores >2 were considered positive). A total of 1077 cases were interpretable for all 3 anti-ER antibodies. ER expression was positive in 68.5% of cases using SP1, in 59.6% using 1D5, and in 58.9% using 6F11. Of 1073 interpretable cases, PR expression was positive in 51.7% of cases. The frequency distribution of Allred scores revealed a bimodal pattern (complete absence of staining or staining in most cells) for both ER and PR. Patients with discordant results for 2 different ER antibodies showed a median overall survival (between that of double-positive cancer and that of double-negative cancer). Our results showed that the rate of hormone receptor expression in breast carcinomas among Korean patients did not differ from that of western patients. In addition, SP1 was the most sensitive antibody for identifying ER expression in tumors. However, further evaluation is needed to determine which antibody is the best for selecting patients with discordant results who are likely to respond to endocrine therapy.

Treatment results of breast cancer patients with locoregional recurrence after mastectomy

Yuri Jeong,Su Ssan Kim,Gyungyub Gong,Hee Jin Lee,Sei Hyun Ahn,Byung Ho Son,Jong Won Lee,Eun Kyung Choi,Sang-wook Lee,Ji Hyeon Joo,Seung Do Ahn 대한방사선종양학회 2013 Radiation Oncology Journal Vol.31 No.3

Purpose: To analyze the results of locoregional and systemic therapy in the breast cancer patients with locoregional recurrence (LRR) after mastectomy. Materials and Methods: Seventy-one patients who received radiotherapy for isolated LRR after mastectomy between January 1999 and December 2009 were retrospectively reviewed. Among the 71 patients, 59 (83.1%) underwent wide excision and radiotherapy and 12 (16.9%) received radiotherapy alone. Adjuvant hormonal therapy was given to 45 patients (63.4%). Oncologic outcomes including locoregional recurrence-free survival, disease-free survival (DFS), and overall survival (OS) and prognostic factors were analyzed. Results: Median follow-up time was 49.2 months. Of the 71 patients, 5 (7%) experienced second isolated LRR, and 40 (56%) underwent distant metastasis (DM). The median DFS was 35.6 months, and the 3- and 5-year DFS were 49.1% and 28.6%, respectively. The median OS was 86.7 months, and the 5-year OS was 62.3%. Patients who received hormone therapy together showed better 5-year DFS and OS than the patients treated with locoregional therapy only (31.6% vs. 22.1%, p = 0.036; 66.5% vs. 55.2%, p = 0.022). In multivariate analysis, higher N stage at recurrence was a significant prognostic factor for DFS and OS. Disease free interval (≤30 months vs. >30 months) from mastectomy to LRR was also significant for OS. The patients who received hormone therapy showed superior DFS and showed trend to better OS. Conclusion: DM was a major pattern of failure after the treatment of LRR after mastectomy. The role of systemic treatment for LRR after mastectomy should be investigated at prospective trials.

속발성 부갑상선 기능항진증의 수술적 치료경험 2예

홍석준,박수길,공병엽 울산대학교 의과대학 1995 울산의대학술지 Vol.4 No.2

Secondary hyperparathyroidism is the condition is which increased parathyroid hormone(PTH) is secreted to compensate for a chronically low calcium level and chronic renal failure is the most common cause. In 1934, Albreight reported an assocition between hyperparathyroidism and the chronic renal failure and in 1960, stanbury first reported subtotal parathyroidectomy in the treatment of secondary hyperparathyroidism. The physiologic mechanisms leading to secondary hyperparathyroidism in the chronic renal failure are well known and relatively well controled with medical management, but sometimes may necessitate surgical intervention in medically intractable cases. In Korea, the surgery of secondry hyperparathyroidism is not frequently done yet as in western countries. We experienced two cases of secondary hyperparathyroidism recently and report its results of subtotal parathyroidectomy.

Treatment results of breast cancer patients with locoregional recurrence after mastectomy

Jeong, Yuri,Kim, Su Ssan,Gong, Gyungyub,Lee, Hee Jin,Ahn, Sei Hyun,Son, Byung Ho,Lee, Jong Won,Choi, Eun Kyung,Lee, Sang-Wook,Joo, Ji Hyeon,Ahn, Seung Do The Korean Society for Radiation Oncology 2013 Radiation Oncology Journal Vol.31 No.3

Purpose: To analyze the results of locoregional and systemic therapy in the breast cancer patients with locoregional recurrence (LRR) after mastectomy. Materials and Methods: Seventy-one patients who received radiotherapy for isolated LRR after mastectomy between January 1999 and December 2009 were retrospectively reviewed. Among the 71 patients, 59 (83.1%) underwent wide excision and radiotherapy and 12 (16.9%) received radiotherapy alone. Adjuvant hormonal therapy was given to 45 patients (63.4%). Oncologic outcomes including locoregional recurrence-free survival, disease-free survival (DFS), and overall survival (OS) and prognostic factors were analyzed. Results: Median follow-up time was 49.2 months. Of the 71 patients, 5 (7%) experienced second isolated LRR, and 40 (56%) underwent distant metastasis (DM). The median DFS was 35.6 months, and the 3- and 5-year DFS were 49.1% and 28.6%, respectively. The median OS was 86.7 months, and the 5-year OS was 62.3%. Patients who received hormone therapy together showed better 5-year DFS and OS than the patients treated with locoregional therapy only (31.6% vs. 22.1%, p = 0.036; 66.5% vs. 55.2%, p = 0.022). In multivariate analysis, higher N stage at recurrence was a significant prognostic factor for DFS and OS. Disease free interval (${\leq}30$ months vs. >30 months) from mastectomy to LRR was also significant for OS. The patients who received hormone therapy showed superior DFS and showed trend to better OS. Conclusion: DM was a major pattern of failure after the treatment of LRR after mastectomy. The role of systemic treatment for LRR after mastectomy should be investigated at prospective trials.

An Examination of the Local Cellular Immune Response to Examples of Both Ductal Carcinoma In Situ (DCIS) of the Breast and DCIS With Microinvasion, With Emphasis on Tertiary Lymphoid Structures and Tumor Infiltrating Lymphoctytes

Kim, Ahrong,Heo, Sun-Hee,Kim, Young-Ae,Gong, Gyungyub,Jin Lee, Hee Oxford University Press 2016 American journal of clinical pathology Vol.146 No.1

Diagnostic accuracy of conventional Pap test, liquid-based cytology and human papillomavirus DNA testing in cervical cancer screening in Korea

Jin-Kyoung Oh(오진경),Hai-Rim Shin(신해림),Gyungyub Gong(공경엽),Jin Hee Sohn(손진희),Shin Kwang Khang(강신광) 한국역학회 2008 Epidemiology and Health Vol.30 No.2

목적: 우리나라에서 자궁경부암 조기검진 방법으로 사용되고 있는 Pap 검사, LBC(액상검사) 및 HPV 검사의 정확도를 파악하기 위함이었다. 연구대상 및 방법 : MEDLINE과 KoreaMed를 통하여 1995년부터 2008년 3월까지 각 검사 방법의 민감도와 특이도를 보고한 논문을 검색하였음. 각 검사 방법의 민감도와 특이도의 대표값을 산출하기 위하여 메타 분석을 실시하였다. 조직학적 확진이 이루어진 사례만 메타 분석에 포함하였으며, CIN2 이상으로 진단된 경우를 질병으로 정의하였다. 세포 검사에서는 ASCUS 이상을 양성으로 간주하였다. 연구성적 : 총 24편의 논문이 검색하였고, 이 중 Pap 검사는 15편, LBC는 3편, HPV 검사는 4편이 선정 기준에 부합하여 메타 분석에 포함하였으며, 메타 분석 결과 민감도는 LBC가 가장 높고(92%), HPV 검사(83%)와 Pap 검사(76%) 순이었고, 특이도는 LBC(79%)가 가장 높고, Pap 검사(76%)와 HPV 검사(59%) 순이었다. 그러나 LBC의 민감도(heterogeneity p-value=0.682)를 제외하고는 모두 연구간에 통계적으로 유의한 이질성을 보였다.(p-value<0.0001). 결론: 각 연구의 이질성이 심하여 본 메타 분석 결과가 각 검사 방법의 정확도를 대표한다고 하기에는 제한적이며, 향후 보다 신뢰할만한 자궁경부암 조기검진 방법의 정확도 검증과 더불어 비용-효과 분석도 이루어져야 할 것이다.

Interobserver Variability of Ki-67 Measurement in Breast Cancer

Chung, Yul Ri,Jang, Min Hye,Park, So Yeon,Gong, Gyungyub,Jung, Woo-Hee The Korean Society of Pathologists and the Korean 2016 Journal of Pathology and Translational Medicine Vol.50 No.2

<P><B>Background:</B></P><P>As measurement of Ki-67 proliferation index is an important part of breast cancer diagnostics, we conducted a multicenter study to examine the degree of concordance in Ki-67 counting and to find factors that lead to its variability.</P><P><B>Methods:</B></P><P>Thirty observers from thirty different institutions reviewed Ki-67–stained slides of 20 different breast cancers on whole sections and tissue microarray (TMA) by online system. Ten of the 20 breast cancers had hot spots of Ki-67 expression. Each observer scored Ki-67 in two different ways: direct counting (average vs. hot spot method) and categorical estimation. Intraclass correlation coefficient (ICC) of Ki-67 index was calculated for comparative analysis.</P><P><B>Results:</B></P><P>For direct counting, ICC of TMA was slightly higher than that of whole sections using average method (0.895 vs 0.858). The ICC of tumors with hot spots was lower than that of tumors without (0.736 vs 0.874). In tumors with hot spots, observers took an additional counting from the hot spot; the ICC of whole sections using hot spot method was still lower than that of TMA (0.737 vs 0.895). In categorical estimation, Ki-67 index showed a wide distribution in some cases. Nevertheless, in tumors with hot spots, the range of distribution in Ki-67 categories was decreased with hot spot method and in TMA platform.</P><P><B>Conclusions:</B></P><P>Interobserver variability of Ki-67 index for direct counting and categorical estimation was relatively high. Tumors with hot spots showed greater interobserver variability as opposed to those without, and restricting the measurement area yielded lower interobserver variability.</P>

타액선 종양의 세침흡인 세포학적 소견:조직학적 진단과의 비교

유은실,추광절,김상윤,최기영,공경엽,이인철 울산대학교 의과대학 1993 울산의대학술지 Vol.2 No.1

We reviewed twenty fine needle aspiration biopsies of salivary gland lesions performed between April 1992 and March 1993, which were confirmed by surgical excision. Sixteen cases were benign lesions:10 pleomorphic adenomas, 3 Warthin's tumors, 1 monomorphic adenoma, 1 benign lymphoepithelial lesion and 1 lymphoepithelial cyst. Malignant lesions were four cases:3 mucoepidermoid carcinomas, and 1 malignant mixed tumor. Preoperative fine needle aspiration cytologic findings were compaired with pathologic diagnosis of the surgically resected specimen in all cases. Overall accuracy was 80%. False negativity and positivity were 5% (1 case) and 0%, respectively. Fine needle aspiration biopsy for diagnosis of salivary gland lesion appears to be a simple, safe, and cost saving diagnistic method with relatively high accuracy.

Individual tumorigenesis pathways of sporadic colorectal adenocarcinomas are associated with the biological behavior of tumors

Kim, Jin C.,Cho, Young K.,Roh, Seon A.,Yu, Chang S.,Gong, Gyungyub,Jang, Se J.,Kim, Seon Y.,Kim, Yong S. Wiley (Blackwell Publishing) 2008 CANCER SCIENCE Vol.99 No.7

<P>Clinicopathologic features of sporadic colorectal adenocarcinomas were compared using integrated data from 224 [corrected] patients subjected to curative resection. Individual steps in the tumorigenesis pathway, that is, adenomatosis polyposis coli (APC), Wnt-activated, base excision repair mutations, mismatch repair defects, RAF-mediated, transforming growth factor (TGF)-beta-suppressed, bone morphogenic protein (BMP)-suppressed, and p53 alterations, were examined in terms of genetic and epigenetic changes, as well as protein expression. Genetic and molecular alterations of right colon cancers were distinct from those of left colon and rectal cancers. Rectal cancers showed the attenuated phenotype of left colon cancers. Tumors most frequently displayed either TGF-beta- or BMP-suppressed alterations (81.2%), followed by RAF-mediated alterations (78.6%), and mismatch repair defects (38.4%), constituting a total of 24 integrated pathways. Tumors lacking APC mutations or carrying the RAF alteration (V600E) were frequently associated with lymphovascular invasion and lymph node metastasis (P < 0.05). Poorly differentiated or mucinous adenocarcinomas were generally associated with high level microsatellite instability, Axin2 suppression, TGF-beta1 or BMPR1A suppression, loss of heterozygosity of D18S46 or D18S474, and absence of base excision repair mutations (P < 0.0001-0.05). Early tumor recurrence was significantly correlated with lack of APC mutations (P = 0.036). Moreover, tumors that concurrently displayed APC/Wnt-activated, TGF-beta/BMP-suppressed, and p53 alterations were significantly predisposed to early recurrence (P = 0.026). Our data clearly indicate that particular steps or pathways of colorectal tumorigenesis are closely associated with characteristic clinicopathologic features that, in turn, determine biological behavior, such as tumor growth, invasion, and recurrence.</P>

Comparison of Silver-Enhanced in situ Hybridization and Fluorescence in situ Hybridization for HER2 Gene Status in Breast Carcinomas

Jun Kang,Gui Young Kwon,Young-Hee Lee,Gyungyub Gong 한국유방암학회 2009 Journal of breast cancer Vol.12 No.4

Purpose: Silver-enhanced in situ hybridization (SISH) is a newly developed method to evaluate HER2 gene amplification in invasive breast carcinomas. Most laboratories widely use fluorescence in situ hybridization (FISH) to evaluate the HER2 gene amplification status because FISH is a very sensitive and accurate technique. However, this technique is not the best because it requires specialized equipment and interpretation skills. We compared a new technique of SISH with FISH for assessing HER2 gene amplification in invasive breast carcinomas. Methods: HER2 gene amplification was assessed in 165 cases of invasive breast carcinoma by FISH and SISH with constructing a tissue microarray. The tumors were assessed by the guidelines of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP). Positivity was defined as a HER2/Chromosome 17 ratio greater than 2.2. Negativity was defined if the ratio was less than 1.8. The tumor was considered as equivocal for HER2 gene amplification if the ratio was between 1.8 and 2.2. The HER2 protein status was assessed. Immunostaining for HER2 protein was performed in a Benchmark automatic immunostaining device with using whole tissue sections. Results: There was agreement of the HER2 gene amplification status by SISH and FISH in 162 of 165 cases, which is a concordance rate of 98.2% (κ=0.94). There were three discrepant cases, with two of them being FISH positive and SISH negative (one case was IHC negative and one case was IHC positive) and one case was FISH negative and SISH equivocal. Conclusion: The 98.2% concordance between FISH and SISH meets the ASCO/CAP requirements for test validation of >95% concordance. These results indicate that SISH can be used as an alternative to FISH for assessing the HER2 gene amplification status in breast carcinomas.