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Case Reports
. 2020 Feb 25:32:100554.
doi: 10.1016/j.gore.2020.100554. eCollection 2020 May.

Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma

Silvia Pelligra  1 , Natalia Buza  2 , Pei Hui  2 , Stefania Bellone  1 , Burak Zeybek  1 , Elena Ratner  1 , Peter E Schwartz  1 , Giovanni Scambia  3 , Alessandro D Santin  1
Affiliations
Case Reports

Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma

Silvia Pelligra et al. Gynecol Oncol Rep. .

Erratum in

Abstract

Background: Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer overexpressing HER2/neu in about 30% of cases. Trastuzumab, a humanized monoclonal antibody targeting Her2/Neu, in combination with carboplatin/paclitaxel, is considered the preferred regimen for the treatment of advanced or recurrent HER2/Neu+ USC per NCCN guidelines.

Case: We describe two USC patients with overexpression of HER2/neu at 2+/3+ level by immunohistochemistry and c-erbB2 gene amplification by fluorescence in situ hybridization (FISH) assay that, after an initial clinical response to trastuzumab, developed resistance/progression. Post-treatment biopsy (collected at the time of clinical progression on trastuzumab) demonstrated loss of HER2/neu overexpression in the recurrent/progressing tumor cells in both patients.

Conclusion: Selection of HER2/NEU negative tumor cells may represent a major mechanism of resistance to trastuzumab in USC patients.

Keywords: HER2/neu; Recurrent; Trastuzumab; Treatment-resistant; Uterine serous carcinoma.

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Figures

Fig. 1
Fig. 1
Case 1. Representative immunostains demonstrating strong membranous staining (score 3+) with marked intratumoral heterogeneity (A) and Her2 gene amplification with a Her2/CEP17 ratio of 3.4 (B) before trastuzumab treatment. Her2 staining is only weak, focal (score 1+) in the recurrent tumor after trastuzumab treatment (C) and the Her2/CEP17 ratio is 0.6 (D). (Original magnification A, C: 100×; B, D: 600×).
Fig. 2
Fig. 2
Case 2. Representative immunostains demonstrating moderate membranous staining (score 2+) with intratumoral heterogeneity (A) and Her2 gene amplification with a Her2/CEP17 ratio of 1.8 (B) before trastuzumab treatment. Her2 staining is absent (score 0) in the recurrent tumor after trastuzumab treatment (C) and the Her2/CEP17 ratio is 0.8 (D). (Original magnification A, C: 100×; B, D: 600×).
See this image and copyright information in PMC

References

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