title: PLK-1 Expression is Associated with Histopathological Response to Neoadjuvant Therapy of Hepatic Metastasis of Colorectal Carcinoma.
abstract: Polo-like kinase 1 (PLK1) is a serine/threonine-protein kinase expressed during mitosis and overexpressed in multiple human cancers, including leukemia and also many solid tumors. PLK1 knockdown has been shown to block proliferation of leukemic cell lines and the clonogenic potential of tumor cells grown from patients with cancer. PLK1 inhibition is a promising strategy for the treatment of some tumors. We aim to analyze expression of PLK1 in metastatic colorectal carcinoma. Retrospective analysis of colorectal carcinomas with hepatic metastasis during follow-up receiving neoadjuvant chemotherapy (NAC), based on oxaliplatin. Immunohistochemistry for PLK-1 in paraffin-embedded tissue from the primary and also from the metastasis. 50 patients. 32% showed good histopathological response. 43% of the primaries were positive for PLK1, as opposed to 23.5% of the metastasis. Expression of PLK1 was significantly reduced in metastasis compared with the primaries (p = 0.05), what could be due to therapy or to a phenotypic change of the metastatic nodule. Analysis of the prognostic influence of PLK1 expression showed significant association between PLK1 expression in metastasis and lower overall survival (p = 0.000). We have also found a significant association between PLK1 expression and histopathological response (p = 0.02). All the tumors with high expression of PLK1 showed minor response (11/11). This study shows the association between survival and poor histopathological response to therapy and high expression of PLK1 in metastasis. Our results could open a new therapeutic approach through the inhibition of PLK1.
authors.affiliation: Department of Surgical Pathology, Hospital Clínico San Carlos, C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain. mgg10167@gmail.com.
authors.forename: M J
authors.initials: MJ
authors.lastname: Fernández-Aceñero
authors.affiliation: Department of Surgery, Health Research Institute FJD-UAM, University Hospital Fundación Jiménez Diaz, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Cortés
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital Fundación Jiménez Diaz, Madrid, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Gómez del Pulgar
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital Fundación Jiménez Diaz, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cebrián
authors.affiliation: Department of Surgical Pathology, Hospital Clínico San Carlos, C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Estrada
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital Fundación Jiménez Diaz, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martínez-Useros
authors.affiliation: Department of Surgery, Health Research Institute FJD-UAM, University Hospital Fundación Jiménez Diaz, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Celdrán
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital Fundación Jiménez Diaz, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: García-Foncillas
authors.affiliation: Department of Surgery, Health Research Institute FJD-UAM, University Hospital Fundación Jiménez Diaz, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Pastor
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D000097869:Polo-Like Kinase 1
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1
keywords: Colorectal carcinoma; Hepatic metastasis; Histopathological response; Neoadjuvant therapy; PLK1; Targeted drugs