Concordance Between Immunohistochemistry (IHC) and Silver Situ Hybridization (SISH) in Endometrial Carcinoma Diagnosis: Using HER-2/neu.

BACKGROUND AND OBJECTIVE: Human epidermal growth factor receptor 2 (Her-2/neu) has been demonstrated as biomarker in Endometrial Carcinoma (EC). This study was conducted to assess the concordance between Sudanese women between immunohistochemistry (IHC) and Silver Situ Hybridization (SISH) for EC diagnosis using HER-2/neu. MATERIALS AND METHODS: This was a retrospective cross sectional study performed in the state of Khartoum, Sudan. This research used eighty-eight samples of embedded blocks of formalin fixed paraffin referred to the histopathology lab from 2007-2013. The technique of tissue microarray (TMA) was used in which paraffin blocks were prepared before IHC and SISH were subjected. RESULTS: In this analysis, 88 specimens were previously diagnosed as endometrial adenocarcinoma. The number of Her-2/new oncogene positive cases among Sudanese women by using IHC were (15.9%), however Her-2/neu amplification in EC were 11.5% by using SISH analysis and strong correlation between Her-2/neu IHC and Her-2/neu SISH is existed, since p-value is 0.,000. CONCLUSION: SISH is a reliable technique that can be used for detecting Her-2/neu oncoprotein and it has many advantages over other methods, also SISH can be used as an alternative to FISH technique.

Concordance of immunohistochemistry between core needle biopsy and surgical resection of breast cancer

Background/aim: The purpose of this study was to evaluate the concordance of immunohistochemical (IHC) parameters of breast lesions between the core needle biopsy (CNB) and the surgical resection specimen. Materials and methods: CNB and resection specimens of female patients were retrospectively analyzed. ER, PR, HER-2, and Ki-67 parameters were compared for each patient. A total of 284 cases were assessed. Forty-one and 48 cases were excluded from the HER-2 and Ki-67 examinations, respectively, because the CNBs did not allow for IHC. Results: Concordance rates were 93.3% for ER, 89.4% for PR, 90.1% for HER-2, and 80.9% for Ki-67.Conclusion: CNB is accurate for the evaluation of the surrogate molecular profile of invasive breast cancer despite the heterogeneity of tumors.

The amplification of c-erb-B2 in cancer-free surgical margins is a predictor of poor outcome in oral squamous cell carcinoma.

The tumour subtype, TNM classification, and histopathological data are sometimes not sufficient for understanding and assessing the behaviour of oral cancers. In an attempt to find additional markers of tumour biology and behaviour, this study sought to determine the incidence and consequently the relevance of c-erb-B2, c-Myc, and H-ras gene alterations in tumour-free margins of oral squamous cell carcinoma (OSCC). Fifty samples of OSCC were analyzed for c-erb-B2 and c-Myc amplification by real-time polymerase chain reaction and for H-ras point mutations by sequencing. A relatively high incidence of genetic lesions was detected: 22% of cases had c-erb-B2 and 30% had c-Myc amplification, whilst only 12% harboured H-ras mutations. Kaplan-Meier analysis and the log-rank test showed statistically significant differences in 5-year survival rates and relapse between patients with tumour margins positive for c-erb-B2 amplification and those with margins that were negative (P=0.002). H-ras and c-Myc alterations could not be associated with tumour behaviour. Molecular analysis of margins, targeting cancer genes, could identify additional, independent predictors of risk and outcome in OSCC.

Expression of c-erb-B2 gene in bladder cancer of Egyptian patients and its correlation with p53 and bcl-2.

Urinary bladder cancer is the 9th most common type of cancer and the 13th most common cause of death worldwide. C-erbB-4 is a class of oncogenes plays a role in cancer development. The present work was performed to assess C-erbB-4 oncogene amplification by PCR technology and its correlation with p53 and bcl-2. This study included 50 male patients (10 controls and 40 urinary bladder cancer patients). The bladder cancer patients include 20 specimens diagnosed as transitional cell carcinoma (TCC) and 20 specimens diagnosed as squamous cell carcinoma (SCC). The results revealed that 7 (35%) of both TCC and SCC showed c-erb-B2 gene amplification. 12 (60%) of TCC and 6 (30%) of SCC showed positive expression of p53. 11 (55%) of TCC and 6 (30%) of SCC showed positive Bcl-2 expression. A direct statistically significant association was detected between c-erb-B2 expression and Bcl-2 and p53 expression in TCC and SCC specimens. Seven (35%) of TCC showed c-erb-B2 gene amplification and expression of both p53 and Bcl-2. Five (25%) of the examined SCC specimens showed c-erb-B2 gene amplification and positive expression for both p53 and Bcl-2. The results indicated that a direct statistically significant association was detected in TCC group between amplification of c-erb-B2 gene by PCR and expressionof p53 and Bcl-2 by immunohistochemistry.

Investigation of recurrence risk in laryngeal cancer following laser surgery.

BACKGROUND: The general prognostic factors in larynx tumors are believed to be tumor stage, anatomical location, histological differentiation and the presence of neck metastasis. Effects of tumor invasion to sub-regions of larynx (anterior commissure, ventricle, subglottic space) and over-expression of p53, c-erb-B2 and Ki67 detected immunohistochemically on development of recurrence in patients were investigated in this study. METHODS: Twenty patients (Group 1) in whom recurrence had developed and 20 others (Group 2) without recurrence during follow-up were included in this study. RESULTS: Both the anterior commissure and ventricle involvements were found to be more frequent in patients with recurrence. But statistically significant difference was detected with only ventricular involvement (p=0.025). After Immunohistochemical evaluation none of the 3 immunohistochemical parameters were found to be higher in the recurrence group and not any of them showed a statistically significant difference between two groups. CONCLUSION: Only ventricle involvement may be a predictor factor for recurrence.

Steroid hormone receptors, MIB-1, p53, and c-erb-B2 expression on breast cancer: Comparison of immunohistochemistry on cell block and fine needle aspiration and tissue sample, in northwest Iran.

BACKGROUND: Fine-needle aspiration of breast cancer often provides moderate cellular material that is representative of the tumors. These samples can be used not only for cytological diagnosis but also to obtain information on the prognosis and likely response to therapy by using immunohistochemical staining studies. METHODS: We assessed the degree of correlation between prognostic biologic markers by means immunohistochemistry (IHC) on cytoblock obtained from fine-needle aspiration (FNA) and immunohistochemical determination on their corresponding tissue sample of five markers; steroid hormone receptors, MIB-1 (Ki-67), p53, and c-erb-B-2 (Her2/neu) in 45 mastectomy of breast cancer. RESULTS: Interobserver reproducibility ranged from 93 to 100%, depending on the marker. A good correlation was observed between immunostaining assessment on cytoblock and on their corresponding tumor tissues as follows: Ki-67 (87%), ER (80%), PR (93%), p53 (96%), and c-erb-B-2 (76%). CONCLUSION: We conclude that cytoblock prepared from fine-needle aspiration specimens of breast cancer is a useful and noninvasive procedure when planning neoadjuvant treatment.

Recursive Partitioning Analysis of Mediastinal N2 Lymph Node Involvement with Selected Biological Markers in Operable Non-small Cell Lung Cancer: A Correlative Study.

BACKGROUND: Expressions of various biomarkers in non-small cell lung cancer (NSCLC) have been linked with the prognosis and involvement of mediastinal lymph nodes. METHODS: In this study, we utilized recursive partitioning analysis (RPA) by using P53, c-erb-B2, and P-glycoprotein (PGP) expressions evaluated by immunohistochemistry to estimate retrospectively the likelihood of the occult N2 mediastinal lymph node involvement in patients with operable NSCLC. RESULTS: In univariate tests, immunohistochemical staining of the primary tumor for these 3 markers in 61 patients undergoing surgery revealed no direct relationship with the N2 involvement. However, RPA demonstrated in patients aged <75 and with >/=4 mediastinal lymph nodes removed that, high PGP expression frequency (>/=20%) predicted an increased likelihood of the N2 involvement (46.7%, R(2) = 0.25). Univariate nominal logistic regression analysis revealed that RPA group affiliation, and the number of mediastinal lymph nodes resected (logarithmic transformation) were associated with the metastasis to N2 lymph nodes (chi(2) = 17.59, p = 0.0005, and chi(2) = 2.40, p = 0.0654, respectively). Multivariate analysis confirmed that only RPA group affiliation predicted the N2 involvement (chi(2) = 14.63, p = 0.0022). CONCLUSION: This study shows for the first time that PGP expression of the primary tumor may help to predict the occult N2 mediastinal lymph node involvement in NSCLC. Thus, further research is required to understand whether PGP expression may aid in the decision process for preoperative mediastinoscopy.

Microarray analysis of the relationship between PTEN and prognostic factors in primary breast cancer tissues / 肿瘤

Objective: To construct tissue microarray of breast carcinoma and to investigate the association of hepatocyte-specific phosphatase and tensin homolog (PTEN) protein expression with prognostic factors such as estrogen receptor (ER), progesterone receptor (PR), c-erb B-2, and Ki-67 in primary breast carcinoma. Methods: Tissue microarray of breast carcinoma was constructed. Immunohistochemical staining was used to detect the expression of PTEN, ER, PR, c-erb B-2, and Ki-67 inbreast carcinoma tissues. Results: PTEN was highly expressed in 66 out of 163 breast carcinoma tissues (40.5%). The positive rate of ER, PR, c-erb B-2, and Ki-67 was 51.5%, 35.6%, 34.4%, and 44.8%, respectively. The positive expression level of MN decreased with increase in auxiliary lymph nodes metastasis, histological grading, and TNM staging. They had negative correlations (P < 0.05). The positive expression level of PTEN had no evident correlation with tumor size and onset age. PTEN had positive correlation with the expressions of ER and PR protein (P < 0.01), and had negative correlation with the expressions of c-erb B -2 and Ki-67. Conclusion: There exists some relationships between low or loss of PTEN expression and the imbalanced expression of ER and PR and the growth and prognosis of breast carcinoma. PTEN may be considered as a potential indicator to judge the malignant degree of breast carcinoma. Combined detection of PTEN, ER, PR, c-erb B-2 and Ki-67 have significant importance and practical value for adjuvant therapy of breast carcinoma.

Análisis inmunohistoquímico de P53, CERB-B2, EGFR y PCNA en cáncer gástrico

Diversas anormalidades genéticas han sido reportadas en el desarrollo del carcinoma gástrico. Este trabajo estudia la inmuno expresión de marcadores inmunohistoquímicos: p 53, C-erb-B2, PCNA y EGFR, en 65 casos (37 hombres y 28 mujeres) con edad promedio de 54.5 años con cáncer gástrico precoz y avanzado. Histológicamente de acuerdo a la clasificación Japonesa, 8 casos (12,3%), se reportaron como adenocarcinomas moderadamente diferenciados, 7 (10.8%) como adenocarcinomas poco diferenciados con patrón sólido, 8 (12,3%) adenocarcinomas pobremente diferenciados patrón no sólido, 1 (1,5%) adenocarcinoma papilar, 12 (18,5%) carcinomas con células en anillo de sello y 12 (18,5%) carcinomas mucinosos. Tres lesiones (4,6%) fueron clasificadas como otro tipo de tumores, específicamente linfoepiteliomas. Según la clasificación de Lauren 23 lesiones (35.4%) se reportaron como carcinomas de tipo intestinal, 27 (41,5%) como carcinomas difusos, 1 (1.5%) como carcinoma mixto y en 14 casos (21.5%) los tumores se consideraron como no clasificables. Observándose: 37 casos positivos para p53, 24 con expresión de EGFR, 33 con expresión c-erbB2, y 55 que expresaron PCNA. La expresión de genes supresores, de factores de crecimiento, así como la expresión de marcadores de proliferación celular en el cáncer gástrico, son frecuentes en tumores gástricos avanzados y precoces En este estudio no se encontró correlación entre la expresión de los marcadores inmunohistoquímicos y los estadios clínico-patológicos.

Many genetic abnormalities have been reported in gastric cancer. We study the immunoexpression of p 53, Cerb B2, PCNA and EGFR in different types of gastric cancers. 65 cases (37 men and 25 women) with a rate of 54.5 years old with early and advanced gastric cancer from the records of our institute, 89.2% were advanced cases, 37cases positive to p53, 24 cases positive to EGFR and 55 cases positive to PCNA. Histological diagnosis was made according to the Japanese classification, 8 cases (12%) were moderately differentiated adenocarcinomas, 7(10.8%) poorly differentiated adenocarcinomas with a solid pattern type, 8(12.3%), poorly differentiated adenocarcinoma with a non solid pattern type 1(1.5%), papillary adenocarcinomas 12 (18.5%), signet-ring cell carcinoma and mucinous carcinoma 12 (18.5%). We also found 3(4.6%) lymphoepithelioma. According to Lauren's classification 23(35.4%) cases were intestinal type, 22(41.5%) cases diffuse type, 14(21.5%) not otherwise specified and 1 case mixed (intestinal and diffuse type). The expression of tumor Suppressors Genes, Growth Factors Genes and Proliferative Genes are frequently expressed in gastric cancer, but there are no correlations with clinical and pathological stages in this study.

The Relationship between Abnormal Screening Bone Scintigraphy and Bone Metastasis in Breast Cancer Patients / 한국유방암학회지

PURPOSE: In this study we evaluated the significance of false positive screening bone scintigraphy (BS) in primary invasive breast cancer patients. Lymphatic vessel invasion (LVI), estrogen receptor (ER), progesterone receptor (PR), nuclear grade, histology grade, epidermal growth factor receptor (EGFR) and C-erb-B2 values were examined in terms of their abilities to predict the accuracy of abnormal BS. We also examined the incidence of bone metastasis in primary invasive breast cancer patients according to the 1988 and 2003 AJCC classifications. METHODS: A retrospective review was performed on 2,044 primary invasive breast cancer patients that had received BS screening, and who were treated by mastectomy or breast conserving surgery at the Seoul National University Hospital between Jan 1995 and Jul 2003. Abnormal screening BS results were divided into "less suspicious" and "highly suspicious" groups. Patient's stages according to the 1988 AJCC classification were reclassified according to the 2003 AJCC classification. Bone metastasis was confirmed by further radiological examination or follow-up BS. All statistical analyses were two-tailed. RESULTS: The incidences of bone metastasis and an abnormal screening BS result were 1.7% (35/2,044) and 13.8% (283/2,044), respectively. The false positive rate of screening BS was 87.6% (248/283). LVI was the only significant predictive factor of bone metastasis in 283 of the abnormal BS patients (p <.001). c-erb-B2 showed no significance to predict bone metastasis in the "less suspicious" group, but was Bone is the most common site of distant metastasis in invasive breast cancer at the time of primary diagnosis. The vertebrae are the most common sites of bone metastasis and the ribs, skull, sternum and proximal long bones are also frequently involved. Bone metastases affect 8% of patients marginally significant in the "highly suspicious" group (p = .046). ER, PR, nuclear grade, histology grade, and EGFR showed no significance in terms of predicting the accuracy of an abnormal BS result. The incidences of bone metastasis were 0.6, 1.3 and 7.6% in stages I, II and III, respectively, according to the 1988 AJCC classification, while these incidences were 0.6, 0.7 and 5.8% according to the 2003 AJCC classification. CONCLUSION: The use of screening bone scintigraphy as a routine screening test is hard to justify due to its high false positive rate. LVI may be a useful factor in that it predicts the accuracy of an abnormal BS result. The incidences of bone metastasis in stages II and III were lower for the 2003 AJCC staging system.

Clinical value of cyclooxygenase-2 expression in human breast carcinoma.

PURPOSE: To determine whether COX-2 expression is associated with clinicopathological parameters, including c-erb-B2 overexpression and angiogenesis, and the disease-free survival of patients with operable breast cancer. MATERIALS AND METHODS: Paraffin-embedded tissue samples were selected from 205 patients surgically resected for breast cancer, between 1991 and 1997, and followed-up for at least 4 years. Samples were immunohistochemically stained with antibodies to COX-2, c-erb-B2 and CD34. RESULTS: COX-2 and c-erb-B2 expressions were detected in 118/205 (57.6%) and 58/205 (28.3%) patients, respectively. COX-2 expression was significantly higher in c-erb-B2 positive than c-erb-B2 negative tumors (75.9% vs. 49.7%, p-value 0.001). COX-2 expression was positively correlated with microvessel count (13.3+/-8.0 vs. 6.6+/-7.0, p-value 0.050), but not with other clinicopathological characteristics, including tumor size, involved axillary lymph nodes and estrogen or progesterone receptor status. Although COX-2 expression itself was not a prognostic marker, breast cancer patients with tumors that co-expressed both COX-2 and c-erb-B2 had a poorer 5-year disease-free survival rate than those that did not (60.2% vs. 78.3%, p-value 0.0527). CONCLUSION: Our data suggest that COX-2 expression occurs frequently in c-erb-B2 positive breast cancer, and co-expression of COX-2 and c-erb-B2 may be a useful prognostic marker in patients with operable breast cancer.

Clinical Value of Cyclooxygenase-2 Expression in Human Breast Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To determine whether COX-2 expression is associated with clinicopathological parameters, including c-erb-B2 overexpression and angiogenesis, and the disease- free survival of patients with operable breast cancer. MATERIALS AND METHODS: Paraffin-embedded tissue samples were selected from 205 patients surgically resected for breast cancer, between 1991 and 1997, and followed- up for at least 4 years. Samples were immunohistochemically stained with antibodies to COX-2, c-erb-B2 and CD34. RESULTS: COX-2 and c-erb-B2 expressions were detected in 118/205 (57.6%) and 58/205 (28.3%) patients, respectively. COX-2 expression was significantly higher in c-erb-B2 positive than c-erb-B2 negative tumors (75.9% vs. 49.7%, p-value 0.001). COX-2 expression was positively correlated with microvessel count (13.3+/-8.0 vs. 6.6+/-7.0, p-value 0.050), but not with other clinicopathological characteristics, including tumor size, involved axil lary lymph nodes and estrogen or progesterone receptor status. Although COX-2 expression itself was not a prognostic marker, breast cancer patients with tumors that co-expressed both COX-2 and c-erb-B2 had a poorer 5-year disease-free survival rate than those that did not (60.2% vs. 78.3%, p-value 0.0527). CONCLUSION: Our data suggest that COX-2 expression occurs frequently in c-erb-B2 positive breast cancer, and co-expression of COX-2 and c-erb-B2 may be a useful prognostic marker in patients with operable breast cancer.

Post-transcriptional control of c-erb B-2 overexpression in stomach cancer cells

The growth factor receptor oncogene, c-erb B-2, is frequently overexpressed in the adenocarcinomas of breast, ovary, lung and stomach. Although the mechanism of erb B-2 overexpression is thought as the result of transcriptional upregulation in many primary human carcinomas, expression rate of c-erb B-2 at mRNA level is usually lower than the level of translated protein. We also found that the expression of erb B-2 in SNU-1 stomach cancer cells was greater at post-transcription level (Bae et al., 1993). To explore the underlying mechanism of erb B-2 protein overexpression, we have chosen two cells lines, SNU-1 and SNU-16 where transcription rate of erb B-2 was closely resemble to each other while expressed protein levels were quite different. The synthesis rate of erb B-2 protein in SNU-1 cells was faster than SNU-16 cells while levels of erb B-2 mRNA were found to be similar in both cell lines. The half-life of the expressed erb B-2 protein was not significantly different in both cell lines. Analysis of the 5' untranslated region (UTR) of erb B-2 mRNA (-1approximately-323) showed no sequence abnormality in both cell lines. However, ribonuclease protection assay using cloned 5 UTR sequence revealed that the size of 5' UTR of erb B-2 mRNA which associate with transcription initiation site(s) in SNU-1 cells was longer than that in SNU-16. These results suggest that the increased erb B-2 protein synthesis rate possibly due to the redundant selection of transcription initiation might be a mechanism of erb B-2 overexpression in SNU-1 cells.

CORRELATIONSHIP OF HORMONE RECEPTOR STATUS, p53 MUTATION AND c-erb B-2 OVEREXPRESSION WITH NUCLEAR GRADING IN BREAST CANCERS.

Thirty cases of infiltrating duct carcinoma of the breast were studied for the expression of estrogen receptor (ER) and progesterone receptor (PR) status; p 53 protein mutation and c-erb B2 overexpression. The results were correlated with the morphological differentiation, as determined by the Nottingham's modification of the Bloom-Richardson system. Hormone receptor positivity was seen in 46.67% cases, whereas p 53 mutation and c-erb B2 overexpression were seen in 50.00% and 60.00% cases respectively. In grade II tumours receptor positivity, p53 mutation and c-erb B-2 overexpression were 57.15%, 42.85% and 52.38% respectively. The corresponding figures for grade III tumours were 33.33%, 83.33% and 66.67% respectively. As grade 1 comprised only 3 cases no statistical correlation could be observed. Thus we conclude that receptor positivity declined, whereas p 53 mutation and c-erb B-2 overexpression increased, with increase in tumour grade.

c-erb B2 and p53 Overexpression in Presence of Human Papilloma Virus Type 16/18 Infection in Carcinomas of the Uterine Cervix: Genesis and Clinicopathologic Analysis / 대한산부인과학회잡지

The 43 cases of the primary uterine cervical carcinoma were analyzed for HPV type 16/18 infection and also analyzed for overexpression of p53 and c-erb B2 oncoprotein to evaluate theirs oncogenic and clinicopathologic relationships. HPV type 16/18 infection was examined by polymerase chain reaction(PCR) and the overexpression of p53 and c-erb B2 protein by using immunohistochemical method. The results were as follow: 1. The HPV infection rate in primary uterine cervical carcinomas was 83.7% respectively.The standard clinicopathologic characteristics(age, histologic type, koilocytosis, mitosis, clinical stage, tumor size, cervical invasion depth, lymph node metastasis, parametrial invasion) were nat significantly correlated with HPV type 16/18 infectivity. 2. The overexpression rate of p53 protein was 72.1% and there was no Significant correlation between expression of p53 protein and the Clinicopathologic characteristics. 3. The overexpression of c-erb B2 oncoprotein was 44.2% and there was no significant correlation between the overexpression of c-erb B2 oncoprotein and the clinicopathologic characteristics. 4. There was no significant correlation between HPV type 16/18 infection and overexpression of p53 and c-erb B2 oncoprotein.