title: Doublecortin-like kinase 1 expression associates with breast cancer with neuroendocrine differentiation.
abstract: Doublecortin-like kinase 1 (DCLK1), a microtubule associated kinase, has recently been proposed to be a putative marker for stemness and adverse prognosis in gastrointestinal cancers. However, it is not clear whether the protein also plays similar roles in breast cancer. Here, the expression of DCLK1 was analyzed in a large cohort of invasive breast cancers (IBC) by immunohistochemistry. DCKL1 was associated with favorable clinico-pathologic features, namely lower histologic grade, absence of lymphovascular invasion, fibrotic focus, necrosis and lower pN stage (p≤0.045). Additionally, independent significant correlations were found with estrogen receptor and neuroendocrine markers (p ≤0.019), implicating its relationship with IBC with neuroendocrine differentiation (IBC-NED). In the current cohort, IBC-NED showed worse outcome than luminal cancers without NED (hazard ratio=1.756, p=0.041). Interestingly, within the IBC-NED group, DCLK1 was found to be a good prognostic factor (hazard ratio =0.288, p=0.011). These findings were in contrast to those in gastrointestinal cancers, suggesting different functional roles of DCLK1 in different types of cancers. In clinical practice, NED is not routinely assessed; thus IBC-NED are not well studied. Its poor outcome and significant heterogeneity warrants more attention. DCLK1 expression could aid in the prognostication and management of this special cancer subtype.
authors.affiliation: Department of Pathology, The Affiliated Baoan Hospital of Southern Medical University, Shenzhen, China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Julia Y S
authors.initials: JY
authors.lastname: Tsang
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Yun-Bi
authors.initials: YB
authors.lastname: Ni
authors.affiliation: Department of Anatomic Pathology, Centro Hospitalar Conde de Sao Januario, Macao, SAR, China.
authors.forename: Thazin
authors.initials: T
authors.lastname: Hlaing
authors.affiliation: Department of Pathology, Kwong Wah Hospital, Hong Kong.
authors.forename: Siu-Ki
authors.initials: SK
authors.lastname: Chan
authors.affiliation: Department of Pathology, Tuen Mun Hospital, Hong Kong.
authors.forename: Kui-Fat
authors.initials: KF
authors.lastname: Chan
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Chun-Wai
authors.initials: CW
authors.lastname: Ko
authors.affiliation: Histopathology Section, Laboratory Department, King Abdullah Medical City, Makkah, Kingdom of Saudi Arabia.
authors.forename: S Shafaq
authors.initials: SS
authors.lastname: Mujtaba
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Tse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D002681:China; D018572:Disease-Free Survival; D000089742:Doublecortin-Like Kinases; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009336:Necrosis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*; D013997:Time Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases
keywords: breast cancer; doublecortin-like kinase 1; neuroendocrine differentiation; prognosis