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Article

Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication

by
Manuela Costantini
1,
Carla Azzurra Amoreo
2,
Liborio Torregrossa
3,
Greta Alì
3,
Enrico Munari
4,5,
Carmen Jeronimo
6,7,
Rui Henrique
6,7,
Sara Petronilho
6,7,
Umberto Capitanio
8,
Roberta Lucianò
9,
Nazareno Suardi
8,
Maria Teresa Landi
10,
Umberto Anceschi
1,
Aldo Brassetti
1,
Vito Michele Fazio
11,12,
Michele Gallucci
13,
Giuseppe Simone
1,†,
Steno Sentinelli
2,*,† and
Maria Luana Poeta
14,*,†
1
Department of Urology, IRCCS Regina Elena National Cancer Institute—Rome, via Elio Chianesi 53, 00144 Rome, Italy
2
Department of Pathology, IRCCS Regina Elena National Cancer Institute—Rome, via Elio Chianesi 53, 00144 Rome, Italy
3
Department of Surgical, Medical, Molecular Pathology and Critical Area, Anatomic Pathology Section, 56126 Pisa, Italy
4
Department of Pathology, Sacro Cuore Don Calabria, 37024 Negrar, Italy
5
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
6
Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), 4200-072 Porto, Portugal
7
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
8
Unit of Urology, Division of Experimental Oncology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, 20132 Milan, Italy
9
Unit of Pathology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
10
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA
11
Laboratory of Molecular Medicine and Biotechnology, University Campus Bio-Medico of Rome, 00128 Rome, Italy
12
CNR-Institute of Translational Pharmacology, 00133 Roma, Italy
13
Department of Urology, University of Rome, La Sapienza, Rome, Viale del Policlinico 155, 00161 Rome, Italy
14
Department of Bioscience, Biotechnology and Biopharmaceutics, University of Bari, via Orabona 4, 70126 Bari, Italy
 
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*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2020, 12(11), 3345; https://doi.org/10.3390/cancers12113345
Received: 4 October 2020 / Revised: 4 November 2020 / Accepted: 10 November 2020 / Published: 12 November 2020
(This article belongs to the Special Issue New Therapeutic Advances in Rare Tumors)
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Simple Summary

Renal collecting duct carcinoma (CDC) is rare, but very aggressive, variant histology of kidney cancers. Besides surgery, the other therapeutic options, such as pharmacological or radiation therapy, have a poor impact on survival. Therefore, there is an urgent need to identify novel targets that can open up new avenues for alternative treatments. From this perspective, the aim of our study was to assess the HER2 protein expression by immunohistochemistry (IHC) and the gene copy number by fluorescence in-situ hybridization (FISH) in a cohort of 26 CDC. According to the 2018 ASCO/CAP guidelines, 2/26 CDC cases (8%) were HER2-positive. The HER2 protein is a well-established target of anti-HER2 mAbs or kinase inhibitors already used for breast and gastric cancer treatment. Thus, this study provides evidence that supports future biomarker-driven clinical trials that could address the lack of therapy, which is still an unmet clinical need for CDC patients.

Abstract

Collecting duct carcinoma (CDC) is rare and aggressive histology of kidney cancers. Although different therapeutic approaches have been tested, the 2-year survival remains very poor. Since CDC exhibits overlapping features with urothelial carcinoma, the analysis of shared molecular alterations could provide new insights into the understanding of this rare disease and also therapeutic options. We collected 26 CDC cases, and we assessed HER2 protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in-situ hybridization (FISH) according to 2018 ASCO/CAP HER2-testing recommendations. Six out of twenty-six (23%) tumors showed HER2 positive staining. In particular, 3+ score was present in 2/6 cases (33%), 2+ in 3/6 cases (50%) and 1+ in 1/6 cases (17%). The 6 HER2+ tumors were also analyzed by FISH to assess gene copy number. One out of six CDC with IHC 3+ was also HER2 amplified, showing an average HER2 copy number ≥4.0 (10.85) and a HER2/CEP17 ratio ≥ (5.63), while the 5/6 cases were HER2 negative. Based on the 2018 ASCO/CAP guidelines overall, 2/26 CDC cases (8%) were HER2+. The present study provides evidence for testing, in future studies, HER2 to assess its clinical value as a novel target for the treatment of this highly malignant cancer. View Full-Text
Keywords: renal collecting duct carcinoma; HER2; biomarker; IHC; FISH renal collecting duct carcinoma; HER2; biomarker; IHC; FISH
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MDPI and ACS Style

Costantini, M.; Amoreo, C.A.; Torregrossa, L.; Alì, G.; Munari, E.; Jeronimo, C.; Henrique, R.; Petronilho, S.; Capitanio, U.; Lucianò, R.; Suardi, N.; Landi, M.T.; Anceschi, U.; Brassetti, A.; Fazio, V.M.; Gallucci, M.; Simone, G.; Sentinelli, S.; Poeta, M.L. Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication. Cancers 2020, 12, 3345. https://doi.org/10.3390/cancers12113345

AMA Style

Costantini M, Amoreo CA, Torregrossa L, Alì G, Munari E, Jeronimo C, Henrique R, Petronilho S, Capitanio U, Lucianò R, Suardi N, Landi MT, Anceschi U, Brassetti A, Fazio VM, Gallucci M, Simone G, Sentinelli S, Poeta ML. Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication. Cancers. 2020; 12(11):3345. https://doi.org/10.3390/cancers12113345

Chicago/Turabian Style

Costantini, Manuela, Carla A. Amoreo, Liborio Torregrossa, Greta Alì, Enrico Munari, Carmen Jeronimo, Rui Henrique, Sara Petronilho, Umberto Capitanio, Roberta Lucianò, Nazareno Suardi, Maria T. Landi, Umberto Anceschi, Aldo Brassetti, Vito M. Fazio, Michele Gallucci, Giuseppe Simone, Steno Sentinelli, and Maria L. Poeta. 2020. "Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication" Cancers 12, no. 11: 3345. https://doi.org/10.3390/cancers12113345

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