Evaluation of HER2, p53, bcl-2, topoisomerase II-α, heat shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes

Cardoso, Fátima; Leo, Angelo Di; Larsimont, Denis; Gancberg, David; Rouas, Ghizlane; Dolci, Stella; Ferreira, Fernando; Paesmans, Marianne; Piccart, Martine

doi:10.1023/a:1011182524684

Cited by 76 publications

(50 citation statements)

References 12 publications

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“…31,32 It is interesting to note that, in both patients with discordant results, amplified HER-2 was detected in the primary tumors but not in the metastases. Another study also reported a loss of HER-2 overexpression in 2 of 44 metastases, 8 but several others described a converse pattern [15][16][17]42,43 or full concordance without either loss or gain of HER-2 amplification. 29,44,45 Together, these findings indicate that the HER-2 gene, although involved in initiating breast oncogenesis, does not appear to be linked directly with tumor dissemination.…”

Section: Discussionmentioning

confidence: 98%

Comparison of HER‐2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma

Gong

Booser

Sneige

2005

Cancer

144

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BACKGROUNDAccurate assessment of HER‐2 status is necessary prior to anti‐HER‐2 antibody (trastuzumab) therapy for metastatic breast carcinoma. However, controversy exists regarding whether to assess HER‐2 status in the primary tumor or in metastatic lesions. It is also unclear whether HER‐2 status can change during disease progression or after chemotherapy.METHODSBreast carcinoma samples from 60 women with known HER‐2 status in both primary tumors and paired metastases (locoregional disease, n = 43 patients; distant disease, n = 17 patients) were reviewed retrospectively. Thirty‐two patients underwent chemotherapy before their metastatic lesions were sampled, including 18 patients who received neoadjuvant chemotherapy and 14 patients who received adjuvant chemotherapy. The HER‐2 gene was examined by fluorescence in situ hybridization either in paraffin‐embedded tissue samples (48 primary tumors and 9 metastatic tumors) or in fine‐needle aspirates (12 primary tumors and 51 metastatic tumors). HER‐2 gene amplification was defined as a HER‐2:chromosome 17 signal ratio ≥ 2.0.RESULTSThe HER‐2 status of primary and metastatic tumors agreed in 58 of 60 patients (97%), including 18 (30%) amplified tumors and 40 (67%) nonamplified tumors. A discrepancy in HER‐2 status was observed in specimens from two patients in which HER‐2 amplification was detected in the primary tumor but not the metastatic tumors. In one patient, three foci of tumor nodules were found in the same breast; the HER‐2 status was assessed in only one of them, which showed amplification; however, HER‐2 amplification was not detected in the axillary lymph node metastasis. In another patient, the HER‐2 gene was amplified in the primary tumor but not in the liver metastasis. No metastases showed HER‐2 amplification without amplification in the primary tumor. Locoregional and distant metastases demonstrated similar concordance rates with their corresponding primary tumors (98% and 94%, respectively). Complete concordance of HER‐2 status was found between primary tumors prior to chemotherapy and metastases that were sampled after chemotherapy.CONCLUSIONSThe HER‐2 status in breast carcinoma generally was stable during metastasis, whether to locoregional or distant sites. Chemotherapy did not modify the HER‐2 status in metastatic lesions. Therefore, HER‐2 amplification can be evaluated reliably in material from either primary or metastatic tumors in most patients. Further study with larger series is warranted to elucidate the significance of discordant results. Cancer 2005. © 2005 American Cancer Society.

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Section: Discussionmentioning

confidence: 98%

Comparison of HER‐2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma

Gong

Booser

Sneige

2005

Cancer

144

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“…Controversial opinions exist both about the stability of HER-2 status in breast carcinoma throughout the course of the disease, and about whether chemotherapy (neoadjuvant or adjuvant) can modify HER2 status. Most data have shown good overall concordance between primary and metastatic lesions, [9][10][11][12][13][14][15] but some data have demonstrated discordance in up to 20% of cases. 9,12,[16][17][18] These differences could be due to a possible genetic drift or clonal selection for HER-2, which may happen during tumour progression, 16 or to the presence of intratumoural heterogeneity of HER-2 status, [19][20][21] with a clone having enhanced metastatic potential, leading to metastases with different HER-2 status from that of the primary lesion.…”

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confidence: 99%

HER‐2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy

Santinelli

Pisa

Stramazzotti

et al. 2007

Intl Journal of Cancer

134

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In this prospective study, we determined HER-2 status in primary breast invasive carcinomas and in the paired lymph node metastases (synchronous and metachronous), local recurrence and metachronous distant metastases, to verify the percentage of discordant cases. HercepTest TM and Fluorescence in situ hybridization (FISH) were used to determine HER-2 status on 119 cases of primary infiltrating breast carcinoma and paired metastases (45 cases with synchronous lymph node metastases, 9 cases with metachronous lymph node metastases, 30 cases with local recurrence, and 35 cases with metachronous distant metastases). A therapeutically significant HER-2 status discordance was demonstrated between primary carcinoma and synchronous lymph node metastases (6.7%), local recurrence (13.3%) and metachronous distant metastases (28.6%). In the first comparison, there was a normal HER-2 status in primary tumours and HER-2 amplification in paired metastases, in the second the opposite phenomenon was present, and both types of discordance were evident in the third comparison. Considering the cases of local recurrences and metachronous distant metastases all together, 14 out of 65 cases (21.5%) showed a therapeutically significant discordance of HER-2 status between the primary tumour and the paired metachronous recurrence or metastasis (p < 0.001), the 15.4% of cases showing normal HER-2 status in the primary tumour and HER-2 amplification in the neoplastic relapse. For the treatment of metastatic patients, the evaluation of HER-2 status should be performed in neoplastic tissue from metastatic site, whenever possible. This procedure could be also suggested in the patients that are metastatic at the time of diagnosis. ' 2007 Wiley-Liss, Inc.Key words: breast carcinoma; FISH; HER-2/neu; HercepTest TM ; metastasis The HER-2 proto-oncogene is located on chromosome 17q21 and encodes a transmembrane tyrosine kinase protein, which belongs to the epithelial growth factor receptors (EGFRs) family. Overexpression of the receptor or amplification of the HER-2 gene has been identified in 15-25% of invasive breast carcinomas and is very important both for the prognosis, 1 and for the therapy. 2,3 Trastuzumab is a humanized monoclonal antibody, which is used in the therapy of invasive breast carcinomas overexpressing HER-2 protein and/or showing HER-2 gene amplification. Trastuzumab treatment, in combination with chemotherapy, has given very good results, in terms of disease free survival and overall survival times, in patients with metastatic breast cancer 2 ; moreover, the results of recent trials on the efficacy of the drug in an adjuvant regimen have showed excellent results in terms of drastic reduction of the precocious relapses, when combined with chemotherapy. 4,5 Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH) are the techniques recommended for HER-2 determination, according to the algorithm showed in Figure 1. Chromogenic in situ hybridization (CISH) has furnished promising results but is not yet considered an...

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“…Overall HER2 tends to correlate well between primary tumors and metastatic sites but significant variations in discordance rates have been reported (2% -27%) [25]. Cardoso et al studied the correlation of HER2 in primary breast carcinoma and lymph node metastases in a large archival material (n = 370) [11]. In this study the overall percentage of discordant marker status was 2%; however, for the tumors that were lymph-node positive, 15% were negative in the primary tumor.…”

Section: Introductionmentioning

confidence: 68%

“…Assuming that the lymph node metastases represent a migrated fraction of the primary tumor cells, the metastatic cells would, conceivably, share an identical molecular profile [5]. Recent research has shown that the heterogeneity and clonal diversity seen in breast cancer contradict this notion [6]- [11].…”

Section: Introductionmentioning

confidence: 99%

Expression of the Epidermal Growth Factor Receptors and Ligands in Paired Samples of Normal Breast Tissue, Primary Breast Carcinomas and Lymph Node Metastases

Brügmann¹,

Jensen²,

Garne³

et al. 2014

ABCR

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Purpose: In breast cancer, the EGF receptors host an increasing number of therapeutic targets and the interactive mechanisms of actions of the receptors and their ligands justify investigation of the EGF family as an entity. Experimental design: Paired tissue samples of normal breast tissue and primary breast carcinomas were examined in a prospective study of 163 patients. A third sample was obtained from the paired ipsilateral metastatic lymph node from 58 of these patients. The mRNA expression of four EGF receptors (HER1 -HER4) and 11 activating ligands was quantified with real-time RT-PCR. Results: Expression of HER2, HER3, and HER4 mRNA was upregulated in primary carcinomas compared to normal breast tissue while HER1 was downregulated. The mRNA expression of HER3 and HER4 differed between primary breast carcinomas and lymph node metastases whereas there was no difference in the expression of HER1 and HER2. The combination of low HER3 and low HER4 expression in the primary carcinoma was significantly more frequent in lymph node-negative patients as compared to lymph node positive patients. Distinct correlation patterns of the receptors and their corresponding activating ligands appeared in both normal breast tissue and in carcinomas, notably for the HER3 and HER4 receptors and their 3 specific ligands: HB-EGF, NRG2, and NRG4. Conclusion: HER2, HER3, and HER4 showed increased mRNA expression in carcinomas and were positively correlated to each other and to specific activating ligands. Furthermore, low HER3 and HER4 expression in the carcinomas correlated to the absence of lymph node metastases.

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Evaluation of HER2, p53, bcl-2, topoisomerase II-α, heat shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes

Cited by 76 publications

References 12 publications

Comparison of HER‐2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma

Comparison of HER‐2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma

HER‐2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy

Expression of the Epidermal Growth Factor Receptors and Ligands in Paired Samples of Normal Breast Tissue, Primary Breast Carcinomas and Lymph Node Metastases

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