Padrões Morfológicos de Doença e Microambiente Tumoral

Our research is translational and focused on the study of tumor microenvironment in cancer progression and therapeutic responses. 

Our general goal is the use of the morphological pattern of human cancers (phenotype) as mirror of molecular alterations using different strategies from clinical-pathological features to cell culture approaches. We expect to improve cancer diagnosis and patients’ management as well as molecular stratification, prognosis and targeted therapy of gynecological cancers

Research Areas

  • HPV associated cancers: to study the effect of biological agents as initiators of carcinogenesis and tumor promotion, and to evaluate the role of extracellular matrix components and cell signaling molecules as new prognostic molecular markers and therapeutic targets.
  • Endometrial and Ovarian cancer: to explore molecular pathways associated with long survival and EMT features in the development of and therapy response with specially emphasizes in molecular pathways and endometrial carcinomas with EMT features.


  • Build-up of precision medicine platform using patient-derived cell models for prediction of drug efficacy in ovarian cancer patients iNOVA4Health – UID/Multi/04462/2019, funded by FCT/MEC
  • Build-up of precision medicine platform using patient-derived cell models for prediction of drug efficacy in ovarian cancer patients
    iNOVA4Health supporting. Tracking Number: 34 PD/BD/128377/2017 (75 000€)
    Principal investigator: Ana Félix and Inês Isidro
  • DREAM-Dendrimer-based Report-Eradication Antineoplasic Machines. Projeto financiado pela FCT (PTDC/MEC-ONC/29327/2017; CQFM- IN and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa) (225 000€)
    Principal investigator: Vasco Bonifácio
  • Long survival in patients with high-grade serous carcinoma of the ovary: a molecular and clinical study
    AstraZeneca, Tracking Number: NCR-17-12893 (40 000€)
    Principal investigator: Ana Félix
  • "Infecção pelo Vírus Papiloma Humano e cancerigénese do colo do útero- factores biológicos na transformação e progressão neoplásicas" Fundação Calouste Gulbenkian
  • “Saúde e Ambiente” in 2005
  • "Cell and molecular alterations in ovarian cancer cells induced by vorinostat therapy, identification of biomarkers for therapy response", Departamento de Anatomia Patológica, FCM-CEDOC-UNL, financiado pelo CEDOC
  • "Unravelling the role of JAK-STAT pathway inhibition in Solid Neoplasia and the impact of p53 mutational status", IPOLFG/CEDOC
  • Ovarian cancer a suitable model to define metabolic profile as a tool to predict chemoresistance. CEDOC/IPOLFG/IBET
  • Molecular mechanisms of cell migration and invasion: developing a new strategy to impair tumor progression, CEDOC/IPOLFG
  • Biomarkers and new therapeutic targets in cervical invasive carcinoma - 2014 Terry Fox, financiado pela Liga Portuguesa Contra o Cancro


  • Brito MJ, Sequeira P, Silva I, Quintas A, Martins C, Félix A. CD4+ and CD8+ cell populations in HIV-positive women with cervical squamous intra-epithelial lesions and squamous cell carcinoma. Int J Infect Dis. 2021 Feb;103:370-377. doi: 10.1016/j.ijid.2020.10.083. Epub 2020 Nov 3. PMID: 33157285
  • Palma Dos Reis C, Correia L, Jorge AF, Félix A. Primary vaginal cancer associated with HPV 68: A case report of an unusual presentation. Int J Gynaecol Obstet. 2021 Feb;152(2):262-263. doi: 10.1002/ijgo.13361. Epub 2020 Sep 14. PMID: 32862465
  • Ferreira J, Félix A. Carcinosarcoma (MMMT). website. Accessed July 27th, 2020
    Medeiros-Fonseca B, et al. HPV16 induces penile intraepithelial neoplasia and squamous cell carcinoma in transgenic mice: first mouse model for HPV-related penile cancer. J Pathol. 2020. 251, 4, 411-419.
  • Gil da Costa RM, Neto T, Estêvão D, Moutinho M, Félix A, Medeiros R, Lopes C, Bastos MMSM, Oliveira PA. Ptaquiloside from bracken (Pteridium spp.) promotes oral carcinogenesis initiated by HPV16 in transgenic mice. Food Funct. 2020. 11(4):3298-3305. doi: 10.1039/d0fo00207k
    André S, Nunes SP, Silva F, Henrique R, Félix F, Jerónimo C. Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer. Int J Mol Sci. 2020. 21, 8, 2715.
  • Bargão Santos P, Lobo J, Félix A, Silva F, Manso RT, Costa JO, Lourenço B, Sequeira JP, Jerónimo C, Patel HHR, Henrique R. The inflammation-related biomarker CXCR7 independently predicts patient outcome after radical prostatectomy. Urol Oncol. 2020 Oct;38(10):794.e17-794.e27. doi: 10.1016/j.urolonc.2020.03.004. Epub 2020 Apr 9.
  • Mestre VF, Medeiros-Fonseca B, Estêvão D, Casaca F, Silva S, Félix A, Silva F, Colaço B, Seixas F, Bastos MM, Lopes C, Medeiros R, Oliveira PA, Gil da Costa RM. HPV16 is sufficient to induce squamous cell carcinoma specifically in the tongue base in transgenic mice. J Pathol. 2020 May;251(1):4-11. doi: 10.1002/path.5387. Epub 2020 Mar 10.
  • Esteves G, Ferreira J, Afonso R, Martins C, Zagalo C, Félix A. HDAC Overexpression in a NUT Midline Carcinoma of the Parotid Gland with Exceptional Survival: A Case Report. Head Neck Pathol. 2020 Jan 27. doi: 10.1007/s12105-020-01130-6. Epub ahead of print.
  • Esteves GF, Félix A. Dermal nerve sheath myxoma. website Accessed January 9th, 2020
  • Santos PB, Patel H, Henrique R, Félix A. Can epigenetic and inflammatory biomarkers identify clinically aggressive prostate cancer? World J Clin Oncol. 2020 Feb 24;11(2):43-52. doi: 10.5306/wjco.v11.i2.43.
  • Bennett JA, Ritterhouse LL, Furtado LV, Lastra RR, Pesci A, Newell JM, Burandt E, Kooreman L, Van de Vijver K, Krausz T, Felix A, Zannoni GF, Young RH, Oliva E. Female adnexal tumors of probable Wolffian origin: morphological, immunohistochemical, and molecular analysis of 15 cases. Mod Pathol. 2020 Apr;33(4):734-747. doi: 10.1038/s41379-019-0375-9. Epub 2019 Oct 7.
  • Lérias S, Esteves S, Silva F, Cunha M, Cochicho D, Martins L, Félix A. CD274 (PD-L1), CDKN2A (p16), TP53, and EGFR immunohistochemical profile in primary, recurrent and metastatic vulvar cancer. Mod Pathol. 2020 May;33(5):893-904. doi: 10.1038/s41379-019-0429-z. Epub 2019 Dec 16.
    Cotzia P, Benayed R, Mullaney K, Oliva E, Felix A, Ferreira J, Soslow RA, Antonescu CR, Ladanyi M, Chiang S. Undifferentiated Uterine Sarcomas Represent Under-Recognized High-grade Endometrial Stromal Sarcomas. Am J Surg Pathol. 2019 May;43(5):662-669. doi: 10.1097/PAS.0000000000001215
  • Casalou C, Faustino A, Silva F, Ferreira IC, Vaqueirinho D, Ferreira A, Castanheira P, Barona T, Ramalho JS, Serpa J*, Félix A*, Barral DC. Arl13b Regulates Breast Cancer Cell Migration and Invasion by Controlling Integrin-Mediated Signaling, Cancers 2019, Sep 29;11(10). pii: E1461. doi: 10.3390/cancers11101461. *Equal contribution
  • Lopes-Coelho F, André S, Félix A, Serpa J. (2017) Breast cancer metabolic cross-talk: Fibroblasts are hubs and breast cancer cells are gatherers of lipids. Mol Cell Endocrinol. 2017 Jan 21. pii: S0303-7207(17)30044-8. doi: 10.1016/j.mce.2017.01.031. 
  • Alemany L, Cubilla A, Halec G, Kasamatsu E, Quirós B, Masferrer E, Tous S, Lloveras B, Hernández-Suarez G, Lonsdale R, Tinoco L, Alejo M, Alvarado-Cabrero I, Laco J, Guimerà N, Poblet E, Lombardi LE, Bergeron C, Clavero O, Shin HR, Ferrera A, Felix A, Germar J, Mandys V, Clavel C, Tzardi M, Pons LE, Wain V, Cruz E, Molina C, Mota JD, Jach R, Velasco J, Carrilho C, López-Revilla R, Goodman MT, Quint WG, Castellsagué X, Bravo I, Pawlita M, Muñoz N, Bosch FX, de Sanjosé S; HPV VVAP study group. Role of Human Papillomavirus in Penile Carcinomas Worldwide. Eur Urol. 2016 Jan 4. pii: S0302-2838(15)01215-4. doi: 10.1016/j.eururo.2015.12.007. PMID: 26762611
  • Silva LS, Goncalves LG, Silva F, Domingues G, Maximo V, Ferreira J, Lam EW, Dias S, Felix A, Serpa J. (2015) STAT3:FOXM1 and MCT1 drive uterine cervix carcinoma fitness to a lactate-rich microenvironment. Tumour Biol. 2015 Nov 12.
  • Cavaco BM, Santos R, Félix A, Carvalho D, Lopes JM, Domingues R, Sirgado M,Rei N, Fonseca F, Santos JR, Sobrinho L, Leite V. Identification of de novogermline mutations in the HRPT2 gene in two apparently sporadic cases with challenging parathyroid tumor diagnoses. Endocr Pathol. 2011 Mar;22(1):44-52.PubMed PMID: 21360064.
  • de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B,et al. Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010 Nov;11(11):1048-56. Epub 2010 Oct 15. PubMed PMID: 20952254.
  • Félix A, Nogales FF, Arias-Stella J. Polypoid endometriosis of the uterinecervix with Arias-Stella reaction in a patient taking phytoestrogens. Int JGynecol Pathol. 2010 Mar;29(2):185-8. PubMed PMID: 20173505.

Book Chapters

  • Felix A, (responsible author), et al Chapter Squamous cell carcinoma, HPV-independent, of the vagina. In WHO Classification of Tumours, Volume on Female Genital Tumours, 5th edition, Lyon, IARC, 2020
  • Felix A, (responsible author), et al Chapter Squamous cell carcinoma, HPV-associated, of the vagina. In WHO Classification of Tumours, Volume on Female Genital Tumours, 5th edition, Lyon, IARC, 2020
  • Stolnicu S, Felix A (co-author), McCluggage W. Glenn Chapter Adenosquamous and mucoepidermoid carcinomas of the uterine cervix In WHO Classification of Tumours, Volume on Female Genital Tumours, 5th edition, Lyon, IARC, 2020
  • Carla Oliveira – IPATIMP, FMUP
  • Carmem Jerónimo - Instituto Português de Oncologia do Porto, Francisco Gentil
  • Catarina Brito - IBET, UNL
  • Inês Isidro – IBET, UNL
  • Esther Oliva – Massachusetts General Hospital, Boston, USA
  • Jaume Ordi – Hospital Clinic, Barcelona, Spain
  • Rui Gil da Costa - LEPABE, Dept. de Engenharia Química, Universidade do Porto (FEUP)
  • José Paulo Santos - NOVA School of Science and Technology; UNL
  • José Rueff – Centre for Toxicogenomics and Human Health (ToxOmics) NOVA Medical School
  • Margarida Silveira - Instituto Português de Oncologia de Lisboa, Francisco Gentil

- Vasco Bonifácio - Instituto Superior Técnico da Universidade de Lisboa

- Simona Stolnicou –University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, Romania

Investigador Principal

Ana Félix
Principal Investigator


Fernanda Silva
Researcher, MD
Saudade André
Researcher, MD
Daniel Gomes Pinto
PhD Student, MD
Daniela Cochicho
PhD Student
Joana Ferreira
PhD Student, MD
Delfim Doutel
Junior Researcher, MD
Sara Mata
PhD Student, MD