In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.
Adult ; Aged ; Amphiregulin ; Betacellulin ; EGF Family of Proteins ; Epidermal Growth Factor ; metabolism ; Epiregulin ; Female ; Gene Expression Profiling ; Glycoproteins ; metabolism ; Heparin ; metabolism ; Heparin-binding EGF-like Growth Factor ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Keratinocytes ; metabolism ; Leukoplakia, Oral ; metabolism ; Lichen Planus, Oral ; metabolism ; Ligands ; Male ; Middle Aged ; Mouth Mucosa ; metabolism ; Nerve Growth Factors ; Neuregulins ; metabolism ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptor, ErbB-3 ; metabolism ; Receptor, ErbB-4 ; Receptors, Cell Surface ; metabolism ; Transforming Growth Factor alpha ; metabolism ; Up-Regulation ; physiology

OBJECTIVE: To explore expression of ErbB3 and ErbB4 genes in laryngeal squamous cell carcinomas and their relation with the biological and clinicopathological parameters. METHOD: Expression of ErbB3 and ErbB4 mRNA in 36 cases of laryngeal carcinomas and normal mucosa of incisal margin, 11 cases of benign proliferative lesions were examined by reverse transcription polymerase chain reaction (RT-PCR). RESULT: In laryngeal carcinomas and benign proliferative lesions, over-expressive positive ratios of ErbB3 were 66.7%, 18.2% respectively (P < 0.01). However, that of ErbB4 were 25.0%, 9.1% respectively (P > 0.05). Differences of expressive level of ErbB3 and ErbB4 were not significant between laryngeal carcinoma and normal mucous of incisal margin (P > 0.05). In addition, expressive level of ErbB3 and ErbB4 were not associated with diversity of clinical pathologic characters (P > 0.05). CONCLUSION ErbB3 and ErbB4 genes play different role in carcinogenesis and development, and relate to the reoccurrence of carcinoma.
Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; ErbB Receptors ; genetics ; metabolism ; Female ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; RNA, Messenger ; genetics ; Receptor, ErbB-3 ; genetics ; metabolism ; Receptor, ErbB-4

PURPOSE: The androgen receptor (AR) plays a central role in prostate cancer. Evidence from several groups indicates that epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) may enhance AR activity in prostate cancer cell lines. This study was designed to investigate the protein expression of AR, EGFR, and HER2 and to determine whether the EGFR and HER2 genes are amplified in prostate cancer tissues. MATERIALS AND METHODS: The protein expression levels of AR, EGFR, and HER2 in a tissue microarray block of 66 prostate cancer samples were investigated by immunohistochemical analysis and chromogenic in situ hybridization was used to determine whether the EGFR and HER2 genes were amplified in these tissues. RESULTS: The AR and EGFR proteins were expressed in 59.1% and 40.9% of prostate cancers, respectively, but their expression levels were not significantly associated with clinicopathologic factors. Of the cases in which tissues were negative for EGFR protein expression, 69.2% were positive for AR protein expression; however, AR protein expression was significantly reduced (44.4%) in tissues in which EGFR protein was expressed. HER2 expression was detected in only 1 case (1.5%). No amplification of the EGFR or HER2 genes was found in prostate cancer specimens. CONCLUSION: This study was limited by small number of subjects, but it can still be inferred that the expression levels of the AR and EGFR proteins are inversely correlated in prostate cancer patients. The potential utility of EGFR and HER2 as prognostic factors or therapeutic targets warrants further study.
Cell Line ; Genes, erbB-2 ; Humans ; In Situ Hybridization ; Prostate ; Prostatic Neoplasms ; Proteins ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Receptors, Androgen

BACKGROUND: To elucidate the clinicopathologic features and their implications on the immunohistochemistry in cases of molecular apocrine breast cancer (MABC). METHODS: Immunohistochemical (IHC) staining for estrogen receptor (ER), human epidermal growth factor receptor 2 (HER-2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR), androgen receptor (AR), gamma-glutamyltrasferase 1 (GGT1) and Ki-67 was performed on tissue microarray breast cancer samples from 204 patients. Phenotypes of breast cancer were divided based on the IHC status of ER, AR and GGT1 into the following: luminal type, ER positive and AR and/or GGT1 positive; basal type, ER, AR, and GGT1 negative; non-basal type, ER positive and AR and GGT1 negative; and MABC type, ER negative and AR and/or GGT1 positive. RESULTS: In our series of patients (n=204), there were 26 cases of MABC. Besides, there were 18, 60, and 100 cases of luminal type, basal type and non-basal type, respectively. The MABC demonstrated apocrine histology and a higher prevalence of HER-2 positivity than other phenotypes. With the basal type, the MABC manifested a more frequent expression of CK5/6 and EGFR and a higher Ki-67 index than other phenotypes (p<0.001). There were no significant differences in patient prognosis between the phenotypes of breast cancer. CONCLUSIONS: MABC are distinguishable from other phenotypes based on the apocrine histology and a higher expression rate of HER-2.
Breast ; Breast Neoplasms ; Estrogens ; Humans ; Immunohistochemistry ; Keratins ; Phenobarbital ; Phenotype ; Prevalence ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Receptors, Androgen

PURPOSE: Preclinical studies have shown that human epidermal growth factor receptor 2 (HER2) status is associated with resistance to radiotherapy (RT). In this study, we evaluated the overall survival of a T1N0M0 breast cancer cohort in Korea according to the use of RT and the HER2 status. METHODS: We analyzed data collected from 11,552 patients with invasive breast cancer who were enrolled in the Korean Breast Cancer Society Registration Program between 1999 and 2007. Data on the TNM stage, estrogen receptor status, progesterone receptor status, HER2 status, operation method, and the use of RT were analyzed. RESULTS: The median follow-up period was 51 months. A significant improvement in overall survival after RT was observed only in the HER2(-) group. In this group, the 10-year overall survival rate was 95.5% for patients who did not receive RT and 96.3% for patients who received RT (p=0.037). In contrast, in the HER2(+) group, RT was not associated with a survival benefit (p=0.887). Multivariate analysis showed that RT was significantly associated with a reduction in mortality in the HER2(-) group (hazard ratio, 0.738; 95% confidence interval, 0.549-0.993; p=0.045). CONCLUSION: We found that postoperative RT was not associated with a survival benefit in HER2(+) breast cancer patients, suggesting that HER2(+) breast cancers could be RT resistant.
Breast ; Breast Neoplasms ; Cohort Studies ; Epidermal Growth Factor ; Estrogens ; Follow-Up Studies ; Humans ; Korea ; Multivariate Analysis ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Receptors, Progesterone ; Survival Rate

PURPOSE: The aim of the current study was to determine the incidence, clinical presentation, and treatment outcomes of "bone-only metastases" in patients with breast cancer and to analyze the impact of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status on prognosis. MATERIALS AND METHODS: Between 1994 and 2007, of 968 patients with metastatic breast cancer who underwent palliative management at Samsung Medical Center, 565 (57%) relapsed with distant metastases. Of the 968, 146 (15%) had bone-only metastases during a median follow-up period of 75 months. Among the 146 patients with bone-only metastases, 122 (84%) were relapsed patients after curative surgery and 24 (26%) were initially metastatic cases. RESULTS: The median time from primary surgery to bone-only metastases of the 122 patients was 37 months (95% confidence interval [CI], 27 to 46 months). Bone-only metastases were more common in the HR-positive group than in the other subtypes (85% for HR+; 8.2% for HER2+; 6.8% for triple negative. Among all 146 patients, 75 (51%) were treated with hormone therapy. The median post-relapse progression-free survival was 15 months (95%CI, 13 to 17 months). The median overall survival was much longer in the HR+ patients than the HER2+ and triple negative breast cancer patients with marginal statistical significance (65 vs. 40 vs. 40 months, p=0.077). CONCLUSION: Breast cancer patients with "bone-only metastases" had excellent clinical outcomes. Further study is now warranted to reveal the underlying biology that regulates the behavior of this indolent tumor, as it should identify 'favorable tumor characteristics' in addition to 'favorable preferential metastatic site.'
Biology ; Breast ; Breast Neoplasms ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Neoplasm Metastasis ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Receptors, Estrogen ; Receptors, Progesterone

PURPOSE: To study clinical features and patterns of recurrence after breast-conserving treatment (BCT) for three molecular subtypes of early stage breast cancer. METHODS: The sample studied included 596 patients with T1-2N0-1 breast cancer who received BCT. Three groups were defined by receptor status. Luminal: estrogen receptor (ER) or progesterone receptor (PR) positive; triple negative (TN): ER, PR, and epidermal growth factor receptor-2 (HER2) receptor negative; and HER2 overexpressing: ER and PR negative but HER2 receptor positive. RESULTS: The number of patients in each group was 408 (68.5%), 105 (17.6%), and 83 (13.9%), respectively. The median follow-up period was 79 months. The TN and HER2 subtypes occurred in younger patients (p=0.0007) and had higher nuclear grade and poorer histologic grade (p<0.0001 and 0.0071, respectively). During the follow-up period, locoregional recurrence was detected as the first site of recurrence in 26 (6.4%), 11 (10.5%), and 9 (10.8%) patients in the luminal, TN, and HER2 subtypes, respectively (p=0.1924). Thirty-one (7.6%), 7 (6.7%), and 7 (8.4%) patients in each group had distant metastases as the first sign of recurrence (p=0.8996). Median time to locoregional and distant recurrence was shorter in the HER2 subtype (p=0.0889 and 0.0780, respectively), and the HER2 subtype was significantly associated with poor overall survival (p=0.0009). CONCLUSION: After BCT in Korean women with early stage breast cancer, the patterns of recurrence were not different among the molecular subtypes, although the TN and HER2 subtypes were associated with younger age, higher nuclear grade, and poorer histologic grade.
Breast ; Breast Neoplasms ; Epidermal Growth Factor ; Estrogens ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Neoplasm Metastasis ; Phenobarbital ; Receptor, erbB-2 ; Receptors, Estrogen ; Receptors, Progesterone ; Recurrence

PURPOSE: Luminal-type breast cancer has a good prognosis compared to other types, such as human epidermal growth factor receptor 2 and triple negative types. Luminal-type breast cancer is classified into luminal A and B, according to the proliferation index. We investigated the clinicopathological factors that affect the prognosis of the luminal-type subgroups. METHODS: We reviewed the medical records and the pathologic reports of 159 luminal-type breast cancer patients who were treated between February 2005 and November 2007. We divided luminal-type breast cancer into luminal A and B, according to Ki-67 (cutoff value, 14%) and analyzed the clinicopathologic factors, such as age at diagnosis, intensity score of estrogen receptor and progesterone receptor, histologic grade, and Bcl-2. Moreover, we compared the disease-free survival (DFS) of each group. RESULTS: In the univariate analysis, age (p=0.004), tumor size (p=0.010), lymph node metastasis (p=0.001), and Bcl-2 (p=0.002) were statistically significant factors in luminal-type breast cancer. In the multivariate analysis, lymph node (p=0.049) and Bcl-2 (p=0.034) were significant relevant factors in luminal-type breast cancer. In the subgroup analysis, the increased Bcl-2 (cutoff value, 33%) was related with a longer DFS in the luminal B group (p=0.004). CONCLUSION: In our study, luminal A breast cancer showed a longer DFS than luminal B breast cancer, further, Bcl-2 may be a potent prognostic factor in luminal-type breast cancer.
Breast ; Breast Neoplasms ; Disease-Free Survival ; Estrogens ; Humans ; Lymph Nodes ; Medical Records ; Multivariate Analysis ; Neoplasm Metastasis ; Phenobarbital ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Receptors, Progesterone

BACKGROUND: Micropapillary carcinoma (MPC) is known to have a worse prognosis than the other subtypes of breast cancer. Occasionally, MPC is observed in association with invasive ductal carcinoma not otherwise specified (IDC NOS), as well as mucinous carcinoma. METHODS: We examined the immunohistochemical expression of an estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) in 127 cases of surgically resected MPC or IDC NOS with MPC. Further, we classified these cases based on their immunohistochemical profile. RESULTS: Among the IDC NOS with MPC cases, 47 were luminal A (62.7%), 10 were luminal B (13.3%), and 9 were HER2 (12.0%). The MPC cases included 4 luminal A (50.0%), 2 luminal B (25.0%) and 1 HER2 (12.5%) subtypes. Of the mucinous carcinomas with MPC, 4 were grouped as luminal A (57.1%), 1 as luminal B (14.3%), and 2 as HER2 (28.6%) subtypes. However, among the mucinous carcinomas, 33 were categorized as luminal A (89.2%), 3 as luminal B (8.1%), and 1 as HER2 (2.7%) subtype, indicating a low incidence of HER2 subtype as compared to the other subtypes. CONCLUSIONS: The luminal B and HER2 subtypes were prevalent in carcinomas with MPC. This result explains the poor prognosis of breast carcinomas with an MPC pattern.
Adenocarcinoma, Mucinous ; Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Estrogens ; Humans ; Immunohistochemistry ; Incidence ; Mucins ; Phenobarbital ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Receptors, Progesterone

BACKGROUND: Triple negative breast cancer (TNBC) is defined as a lack of the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in breast cancer. Many TNBCs show a profound infiltration of tumor infiltrating lymphocytes (TILs). It is still uncertain whether these TILs are protumoral or antitumoral. Regulatory T cells (Tregs) play a role in inducing immune tolerance to antigens, and they may be selectively recruited by cancer cells. This study was conducted to evaluate the significance of TILs with an emphasis on forkhead box p3 (Foxp3), which is a marker for CD25+CD4+ Treg in TNBC. METHODS: We investigated the Foxp3, CD8 and CD4 expressions in 100 cases of TNBC by immunohistochemistry and using a tissue microarray. The Foxp3 expression was divided as the high and low infiltration groups (cut-off value=20). RESULTS: The high infiltration group was correlated with higher histologic and nuclear grades. However, Foxp3+ Tregs were decreased in the T3 and T4 TNBCs as compared to that of the T1 and T2 TNBCs. No significant differences were found for the nodal status, lymphovascular invasion, stage, recurrence and overall survival. CONCLUSIONS: High Foxp3+ Treg infiltration in TNBC is correlated with the nuclear and histologic grades, but there was no relation to recurrence and overall survival.
Breast ; Breast Neoplasms ; Estrogens ; Forkhead Transcription Factors ; Humans ; Immune Tolerance ; Immunohistochemistry ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Receptors, Progesterone ; Recurrence ; T-Lymphocytes, Regulatory