HER-2/ NEU expression

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HER 2 neu Expression in Colorectal Adenocarcinoma and Its Correlation with Clinicopathologic Variables

HER 2 neu Expression in Colorectal Adenocarcinoma and Its Correlation with Clinicopathologic Variables

This is to certify that the dissertation entitled “HER 2 neu expression in colorectal adenocarcinoma and its correlation with clinicopathologic variables” is a record of bonafide work done by Dr.N.VANI in the Department of Pathology, Coimbatore Medical College, Coimbatore under the guidance and supervision of Dr.V.PRABA, M.D., Associate Professor, Department of Pathology, Coimbatore Medical College and submitted in partial fulfilment of the requirements for the award of M.D. Degree (Branch III) in Pathology by The Tamilnadu Dr. MGR Medical University, Chennai.
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Original Article Evaluation of p16 and HER-2/neu expression in Adenocarcinoma of uterine cervix- A study from tertiary health care center

Original Article Evaluation of p16 and HER-2/neu expression in Adenocarcinoma of uterine cervix- A study from tertiary health care center

Results: A total of 33 cases of adenocarcinoma cervix were observed in the present study. Positive p16 expression with variable intensity was noted in all the cases. HER-2/neu was strongly expressed in only 4 cases (12%) of Adenocarcinoma cervix. However, positivity was associated with all cases showing parametrial extension and all these cases were histologically diagnosed as high grade. Although statistically significant correlation between HER-2/neu expression, stage of tumor, presence of lympho- vascular invasion and nodal metastasis could not be established but cases with high grade of the tumor and parametrial extension did show strong immunoreactivity with HER-2/neu oncoprotein.
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Role of microvessel density, HER-2/ NEU expression and CD-34 in prognostication and grading of bladder carcinomas.

Role of microvessel density, HER-2/ NEU expression and CD-34 in prognostication and grading of bladder carcinomas.

pre-existing blood vessels. The process of neovascularization in tumours is regulated by the combined action of tumour cells, stromal cells and inflammatory cells. (38) Neovascularisation is essential for both benign and malignant tumours especially when it grows beyond 2 mm 3 . Microvessel density has been shown to add to prognostic information in a number of solid tumours including prostate (Weidner et al, 1993), colon (Takahashi et al, 1995), lung (Mattern et al, 1996) and breast cancer (Linderholm et al, 1999). Microvessel density, has also recently been proven to add prognostic information in bladder carcinoma. However, contradictory results have also been reported; (39) this may be due to significant differences in the methods employed for sample selection, techniques of immunostaining, counting of vessels and statistical analysis, although a number of biological differences may account for the discrepancy.
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Evaluation of HER-2/neu status in Gastric Carcinoma

Evaluation of HER-2/neu status in Gastric Carcinoma

In contrast to breast cancer where IHC for HER-2/neu is usually homogenous, tumour heterogeneity is more common in gastric cancer. Heterogeneous staining can sometimes be seen within one gland. The most important reason for heterogeneous staining, however, is that up to one third of gastric cancers are of mixed intestinal/diffuse type. Strong staining is often seen in areas of an intestinal type of differentiation, while areas of diffuse types of differentiation are negative. (34) Signet ring cell carcinomas are almost always negative. An identical heterogeneous pattern of staining is identified at the DNA level (amplification). Because of heterogeneity, the 10% cut-off level for positivity, which is required in breast cancer, is omitted in gastric cancer. Positivity in gastric cancer specimens is thus independent of the percentage of stained cells and it is sufficient to have a cohesive group of cells displaying HER-2/neu positivity. The heterogeneity of HER-2/neu overexpression / amplication is difficult to explain from the biologic point of view the mechanisms leading to silencing HER-2/neu expression in an area of a tumor with homogeneous HER-2/neu amplification, is at present unknown. (32)
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Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women

Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women

Scoring for proportion staining was as follows: 0 denotes no nuclear staining, 1 denotes ,1% nuclei staining, 2 denotes 1%–10% nuclei staining, 3 denotes 11%–33% nuclei stain- ing, 4 denotes 34%–66% nuclei staining, and 5 denotes 67%–100% nuclei staining. Scoring for staining intensity was as follows: 0 denotes no staining, 1 denotes weak staining, 2 denotes moderate staining, and 3 denotes strong staining. The score for proportion staining multiplied by the score for staining intensity is equal to the score. Score 0 indicates that endocrine treatments or tamoxifen will definitely not work and such patients should receive an alternative first-line treatment. Score 2–3 indicates a 20% chance of response to endocrine treatment. Score 4–6 indicates a 50% chance of response to endocrine treatment. Score 7–8 indicates a good (75%) chance of response to endocrine treatment. 0 score is negative, which denotes no staining seen or staining seen in less than 10% of tumor cells. Score 1 + is negative, which denotes that a faint/barely perceptible membrane staining is detected in more than 10% of tumor cells but that the cells are stained in only part of the membrane. Score 2 + shows a borderline or weakly positive result, which denotes that weak to moderate complete membrane staining is seen in more than 10% of tumor cells. Score 3 + is strongly positive, which denotes that strong complete membrane staining is seen in more than 30% of tumor cells. True HER-2/neu positivity is shown by crisp brown-colored membrane staining in at least 30% of the invasive tumor. Score 3 is two steps higher than HER-2/neu expression in surrounding benign breast parenchyma.
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Tumor escape and progression of HER 2/neu negative breast cancer under immune pressure

Tumor escape and progression of HER 2/neu negative breast cancer under immune pressure

invasive HER-2/neu positive or negative breast cancers. Several other correlative or in vitro studies suggest potentially negative effects of some immune responses in breast cancer. Matkowski and Sheu both showed in cohorts of 88 and 24 patients with operable breast can- cer, respectively, that relapse or disease progression was associated with strong CD8+ T cell infiltration [8,9]. Interestingly, it was reported that HER-2/neu+ human prostate tumor cell lines, DU145 and PC-3, that responded to IFN-g (because of the expression of IFN-g Ra), showed down-regulation of HER-2/neu expression whereas another prostate tumor cell line, LNCaP, that failed to respond to IFN-g did not show any change in the expression of HER-2/neu [10]. Such failure of the LNCaP to respond to IFN-g was later shown to be due to the lack of JAK1 expression [11]. These findings prompted us to determine whether HER-2/neu-specific IFN-g producing T cell responses may be associated with HER-2/neu loss and progression to HER-2/neu negative breast carcinoma. To test this hypothesis, we conducted pilot studies in patients with HER-2/neu positive and HER-2/neu negative breast carcinoma to determine whether patients with HER-2/neu negative tumors had HER-2/neu-specific T cell responses that had been induced by HER-2/neu positive pre-malignant lesions in the past.
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HER-2/Neu over-expression in invasive Bladder Cancer in Sudanese Patients

HER-2/Neu over-expression in invasive Bladder Cancer in Sudanese Patients

Previous studies on HER-2 expression in bladder carcinoma using Western blot analysis and IHC have found a correlation between increased HER-2 expression and both higher tumor stage and grade ( 20,21).but our study contradicted these studies, we found no significant correlation between HER-2 over-expression and histological subtype of bladder cancer (TCC, SCC) (p=0.55), and also no significant correlation between HER-2 over expression and tumors grade (P=0.06). Others (16, 19, 22) have reported a significant association between HER-2 over-expression and a higher tumor grade. Thus, shawky et al. ( 23) studied HER-2 over-expression in invasive bladder carcinoma among cohort patients. HER-2 over-expression was associated with high-grade bladder cancers. Similarly, in a recent study ( 24) on 59 patients, HER-2 over-expression was significantly correlated with the differentiation grade, our study contradicted for these studies; we found no significant association between HER-2/Neu expression and the grade of bladder carcinoma(P=0.06).
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Expression and prognostic significance of E Cadherin, EGFR,    p53 and HER-2/NEU in Gastric Carcinoma.

Expression and prognostic significance of E Cadherin, EGFR, p53 and HER-2/NEU in Gastric Carcinoma.

The incidence of gastric carcinoma in the year 2011 in RGGGH was 3.26%. Many patients were older than 55 years of age with male preponderance which is similar to several other studies conducted throughout the world. Females showed a younger mean age of incidence compared to males. 29% of cases showed reduced expression of E Cadherin. A significant association was found between reduced expression of E Cadherin and reduced survival. A significant association of EGFR over expression was found with moderately differentiated grade. No significant association was found between EGFR expression and survival. An increased frequency of cases with p53 positivity showed intestinal type of Lauren‘s classification, moderately and poorly differentiated grades and no association between p53 positivity and survival was found. All the cases which showed HER-2/Neu over expression showed T3 level of infiltration, no association with HER- 2/Neu expression and survival was found.
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Expression of Her-2/neu in Colon Carcinoma and Its Correlation with the Histological Grades and the Lymph Nodes Status

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Results: Her-2/neu was positive in 65% of the cases. It was seen in 68.75% cases of well differentiated, 53.84% cases of moderately differentiated and 100% cases of poorly differentiated conventional adenocarcinomas. Mucinous carcinomas showed more positivity (71.4%)for Her-2/neu as compared to conventional adenocarcin- omas (64.5%). The positivity was more in the grade III tumours as compared to that in the other grades. All the colorectal carcinoma cases with metastatic nodes were positive for Her-2/neu staining. Conclusion: Thus, it was concluded that colorectal carcinomas, especially those with lymph node metastasis, should be subjected to Her-2/neu expression studies, as the tumours which expressed Her-2/neu could carry a poor prognosis and therefore would require a different therapeutic approach, as these cases could respond to Trastuzumab (Herceptin) therapy.
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Effect of neoadjuvant chemotherapy and its correlation with HPV status, EGFR, Her 2 neu, and GADD45 expression in oral squamous cell carcinoma

Effect of neoadjuvant chemotherapy and its correlation with HPV status, EGFR, Her 2 neu, and GADD45 expression in oral squamous cell carcinoma

In our study, all the cases expressed EGFR while Her-2- neu was expressed in 3 (12.5%) out of 24 patients. Her- 2-neu expression was associated with high EGFR expres- sion (correlation coefficient r = 0.4; p = 0.048). Neither EGFR expression nor Her-2-neu expression was signifi- cantly associated with response to CTh with docetaxel (r = 0.321; p = 0.126 and r = 0.378; p = 0.69 for EGFR and Her-2-neu respectively) and with 2-year disease-free and overall survival. In an earlier study, EGFR was expressed in 79.4% of cases of recurrent HNSCC [24]. EGFR-posi- tive tumors had a 3-year cause-specific survival of 27.2% after salvage surgery whereas EGFR-negative tumors had a 3-year cause-specific survival of 64.3% (p < 0.001) [24]. The EGFR expression alone had no significant impact on sur- vival [24]. In another study by Shiraki et al., the overall EGFR expression was 39% and in T3 and T4 lesions, it was 37%. In the same study, co-expression of EGFR, p53, and cyclin D1 was associated with shortened survival [11]. Xia et al. observed that at the combine expression of EGFR, Her-2-neu and Her-3 is a stronger predictor of outcome in oral SCC than any individual family members of the EGFR family [12]. EGFR expression (87.5%) was not found to be associated with proliferation, apoptosis, angiogenesis, and
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Concordance of HER 2/Neu over Expression with Steroid Receptor Status in Female Breast Cancers

Concordance of HER 2/Neu over Expression with Steroid Receptor Status in Female Breast Cancers

In progesterone positive patients, there were 11 (65%) patients HER-2/neu positive, while there were 27% (4) patient HER-2/neu positive among the progesterone negative patients, this finding were statistically significant (P = 0.02) and this was more or less the same like the relation mentioned before between HER-2/neu and estro- gen. It seems that progesterone is under the direct effect of estrogen, or both estrogen and progesterone have the same relation with HER-2/neu expression. Pierce et al. [17] found no relation between ER, PR and HER-2/neu over expression, but in the current study, it is very evident that HER-2/neu over expression follow both estrogen and progesterone as in positive ER and PR there were 52% and 65% positive HER-2/neu, while in negative ER and PR there were 82% and 73% negative HER-2/neu, this finding was statistically significant. These more or less immuno reactivity pattern were more evident in the negative hormone status [18]. It can be stated that breast cancer cells that present with positive steroid hormone receptors with HER-2/neu over expression, may expe- rience no response to anti-steroid therapy, owing to HER-2/neu over expression. This was in pre-herceptin era, now a day the outcome in improving due to the effect of herception [19]. On the other hand, patients with nega- tive steroid hormone receptors and over expression of HER-2/neu, will have wild tumors biologically as they lost the effect of steroid receptors with its partial control on cell division with very aggressive course due to HER-2/neu over expression with early metastasis and recurrence [20] [21].
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HER 2 therapy  HER 2/neu diagnostics in breast cancer

HER 2 therapy HER 2/neu diagnostics in breast cancer

Currently, treatment of MBC patients with HER-2/neu positive tumors is based on HER-2/neu status derived from the primary tumor, which was generally removed many years previously and stored as paraffin-embedded blocks. In a 2005 report by Zidan and coworkers [13] it was pointed out that HER-2/neu status of the primary tumor may not accurately reflect the HER-2/neu status of the metastatic tumor, and that this should be taken into account when making treatment decisions. Those investigators demon- strated 14% discordance between primary and metastatic tumors by IHC. Twelve per cent (7/58) of the patients were HER-2/neu positive in the metastatic tumor yet negative in the corresponding primary tumor. Interestingly, three of the seven patients who were HER-2/neu negative in the primary tumor but positive by IHC in the metastatic tumor responded to trastuzumab-based therapy. The references list of that report directed us to several other papers comparing HER-2/ neu status, as determined using IHC and FISH, between primary breast tumor and metastatic tumor from the same patient. Evidence supporting the observation that a primary breast tumor can be HER-2/neu negative while the metastatic tumor can positive is illustrated below with a few examples. Edgerton and coworkers [14], employing IHC and FISH, reported 20% discordance between the primary and metastatic tumor, which was due to normal HER-2/neu expression in the primary tumor and HER-2/neu over- expression in the metastatic tumor. Gancberg and colleagues [15] compared HER-2/neu status of the primary breast tumor with that of at least one distant metastatic tumor in 107 patients using both IHC and FISH. There was a 6% (6/100) rate of discordance with IHC between the primary and metastatic tumor. In the six cases of discordance, there was greater HER-2/neu staining in the metastatic tumor tissue than in the primary tumor tissue. By FISH analysis, 7% (5/68) of the cases were discordant. Three of the five discordant patient specimens exhibited amplification in the metastatic tumor but not in the primary tumor. It was also reported that if all metastatic tumor sites were included in the analysis, then the HER-2/neu positive metastatic tumors with a corres- ponding negative primary tumor were more frequent than the converse, suggesting that HER-2/neu expression in primary tumors might represent an underestimation of reality. In another study [16], 80 paired primary tumors and metastatic tumors from the same patients were evaluated for HER-2/neu
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Association between HER-2/neu over-expression and clinico-pathologic parameters of breast cancer in northern Malaysia

Association between HER-2/neu over-expression and clinico-pathologic parameters of breast cancer in northern Malaysia

In our study, ER negativity was more strongly associated with HER-2/neu negativity. It was the same with PR negativity. However our study has some limitations. Malaysian population represent a multiracial community with Chinese, Malays and Indians as major racial groups and this biological diversity may be responsible for differences in ER, PR and HER-2/neu expression. Furthermore our results may have been affected by the use of immuno histochemistry analysis of HER-2/neu. Therefore more studies are needed from Malaysia to verify our findings.
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IMMUNOHISTOCHEMICAL EXPRESSION OF CD10 AND HER-2/NEU IN UROTHELIAL CARCINOMA VERSUS CHRONIC CYSTITIS IN ZAGAZIG UNIVERSITY HOSPITALS(RETROSPECTIVE STUDY)

IMMUNOHISTOCHEMICAL EXPRESSION OF CD10 AND HER-2/NEU IN UROTHELIAL CARCINOMA VERSUS CHRONIC CYSTITIS IN ZAGAZIG UNIVERSITY HOSPITALS(RETROSPECTIVE STUDY)

cystitis because their study take a large sample of bilharzial cystitis, with significant difference (p < 0.05) . Overexpression of HER2/neu showed different rank in this study by reason of small sample size. In this study showed variance in overexpression of HER2/neu of high grading UC in relative to low grading UC with statistically significant (p < 0.05), the high grade of urothelial carcinoma showed high overexpression than low grade showed lower expression so the HER2/neu expression was statistically significantly related to the differentiation of tumors . This study was found a significant relationship between expression of HER2/neu score and pathological stage of urothelial carcinoma (P < 0.05). In agreement with several reports [21-27-28-29] whom found that overexpression of HER2 /neu protein correlated with the grade and stage of the urothelial carcinoma . In comparsion with Ioachim et al . [30] who found no relation between her2/neu over expression and the grade and stage of UC (P > 0.05). This difference results due to the heterogeneity between antibodies, protocols, interpretations of HER2/neu expression . In conclusions: Using immunohistochemical method , high expression of CD10 was related to high grade and stage of urothelial carcinoma . HER 2/ neu overexpression was associated with high grade and stage of urothelial carcinoma compared with low grade and stage of UC.
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HER 2/Neu Status in Gastric Carcinomas in a Series of Egyptian Patients and Its Relation to Ki 67 Expression

HER 2/Neu Status in Gastric Carcinomas in a Series of Egyptian Patients and Its Relation to Ki 67 Expression

trial, countries with higher ratios of intestinal: diffuse/mixed cancer had increased HER2/neu-positivity rates [17], as HER2/neu positivity differed significantly by histological subtype (intestinal 34%, diffuse 6%, mixed 20%) [26]. In opposition to previous studies [27] [28], HER2/neu positivity in our series did not relate signifi- cantly with tumor grade. This contradiction may be due to different sample sizes, or differences in the scoring schemes with different cut-off points that were used prior to the establishment of a standard guideline for as- sessing HER2/neu expression. The adoption of the current consistent guidelines for HER2/neu assessment in future studies might clarify this issue.
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A study on role of HER 2/NEU over expression in gastric carcinoma in south Indian population

A study on role of HER 2/NEU over expression in gastric carcinoma in south Indian population

detection (RT-PCR, FISH, quantitative PCR), but costs turn them unavailable for broader use in our hospital. Uchino16 detected 2% positive staining of HER2/NEU protein in poorly differentiated gastric carcinomas where as in our study it is found to be 6%, and Tsujimoto17 found no amplification of HER2/NEU gene in undifferentiated type carcinoma by Western Blot. But in our study we found HER2/NEU expression only in poorly differentiated carcinomas .

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Expression of HER Receptor Proteins in Prostate Adenocarcinoma: A Perspective from North Central Nigeria

Expression of HER Receptor Proteins in Prostate Adenocarcinoma: A Perspective from North Central Nigeria

The exact prevalence of Her2 protein overexpression and gene amplification in Primary PCa remains unclear. In concordance with our findings, researchers at Indiana, in the United States, reported that (Using the standard method), only 1 of 38 cases demonstrated Her2 overexpression while none of the 38 samples displayed Her2 amplification on FISH [7]. Equally 0 of the 147 samples analysed by Visakorpi et al. displayed expression of Her2. However, Ross documented gene amplification in 41% of PCas studied [27] [28] [29] [30]. The likely reason for this variation is a lack of standardized methodology. Most if not all studies assessing Her2 expression in prostate, have employed antibodies and protocols validated for use on other organs such as Breast and Stomach. Some studies have even used polyclonal antibodies, while others have considered cytoplasmic staining as positive. Highly reproducible, organ specific, validated techniques are pivotal, to ensure comparable data across various studies. Another plausible hy- pothesis is that since Her2 has no known ligand, its association with EGFR cell signalling is linked to its ability to form heterodimers with other members of the HER protein family. This “secondary recruitment” might account for its incon- sistent expression [7] [10] [26].
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Zombirt, Ewa
  

(2011):


	Charakterisierung disseminierter Tumorzellen im Knochenmark von Mammakarzinompatientinnen.


Dissertation, LMU München: Medizinische Fakultät

Zombirt, Ewa (2011): Charakterisierung disseminierter Tumorzellen im Knochenmark von Mammakarzinompatientinnen. Dissertation, LMU München: Medizinische Fakultät

Nach dem heutigen Wissensstand werden in der Behandlung von Mammakarzinompatientinnen Prognosefaktoren, wie die Tumorgröße, der axilläre Lymphknotenstatus und das histopathologische Grading als grobe Risikoeinschätzung für das Auftreten eines Rezidivs genutzt. Diese lassen aber keine sicheren Rückschlüsse auf den individuellen Therapieerfolg zu, da sie nur zum Zeitpunkt der Primärdiagnose verfügbar sind. Es besteht also ein hoher Bedarf für einen jederzeit verfügbaren Marker zur Risikoeinschätzung im weiteren Verlauf der Erkrankung und zum Therapiemonitoring. Der Nachweis von Tumorresiduen im Knochenmark und Blut sowie Charakterisierung deren HER- 2/neu-Profils könnte dafür geeignet sein.
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Expression of Her-2/neu in extrahepatic cholangiocarcinoma

Expression of Her-2/neu in extrahepatic cholangiocarcinoma

Her-2/neu-positive breast carcinoma was used as a positive control. For negative control, the primary antibody was omitted during the incubation step. The EHBC-TMA was incubated for 16 min with a Her-2/neu rabbit monoclonal antibody (clone 4B5, using the Benchmark XT; Ventana Medical Systems) and detected by ultraview universal DAB detection kit (using the Benchmark XT; Ventana Medical Systems, Inc.). Antigen retrieval was performed using the Ventana Cell Conditioner #1 for 32 min. The Her-2/neu protein expression was evaluated using the modified ToGA trial scoring criteria established for gastric and gastroesophageal carcinomas 12–14 as follows: 1) no
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VEGFR OVEREXPRESSION AS A PROMISING PREDICTIVE AND PROGNOSTIC BIOMARKER FOR BREAST CANCER

VEGFR OVEREXPRESSION AS A PROMISING PREDICTIVE AND PROGNOSTIC BIOMARKER FOR BREAST CANCER

This study examined 40 tissue biopsies taken from patients diagnosed with breast cancer in H. Adam Malik Hospital Medan, Indonesia. Samples were analyzed by immunohistochemistry to determine the histopathology, grading, lymphovascular invasion and expression of VEGFR, HER-2/neu and ER/PR. Association between dependent and independent variables was conducted using chi-square test and logistic regression.

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