Doublecortin-like kinase 1 (DCLK1), a microtubule linked kinase, has recently been proposed to be a putative marker for stemness and adverse prognosis in gastrointestinal cancers. positive cells displayed improved sphere forming and tumor initiating capacity [10], and enhanced epithelial-mesenchymal transition (EMT), a process closely linked 210344-95-9 manufacture to the acquisition of stem cell properties, via rules of microRNA biogenesis [4, 6, 11]. Interestingly, colorectal malignancy with high DCLK1 manifestation had increased tumor specific mortality [5]. Upregulation of DCLK1 manifestation in blood circulation was found in chemoradiotherapy-treated colorectal malignancy individuals [12]. Aberrant DCLK1 manifestation was recognized in IBC [13]. Knockdown of oncogenic miR-21 in IBC was accompanied by a decrease in DCLK1 manifestation [14]. Apart from these, no additional info is currently available. It is not clear whether the aberrant DCLK1 manifestation contributed to IBC tumor aggressiveness as with gastrointestinal cancers. In addition, CSC heterogeneity is present in different breast tumor subtypes [15], and the commonly used CSC markers did not determine all CSC populations. It will be interesting to explore using DCLK1 like a CSC marker 210344-95-9 manufacture in breast tumor subtypes. In this study, we evaluated the manifestation of DCLK1 in a large cohort of breast tumor by immunohistochemistry (IHC), its association with clinico-pathological features along with other biomarkers (including 210344-95-9 manufacture CSC markers) manifestation, as well as the relationship with breast cancer outcome. RESULTS A total of 1132 instances were included in this cohort. The mean individuals’ age was 54.612.7 (range 22-97) years. The mean tumor size was 2.671.52 (range 0.2-13.9) cm. One hundred and seventy three instances (15.3%) were grade I, 457 instances (40.4%) were grade II and 502 instances (44.3%) were grade III. Nine hundred and eighty seven instances were IBC of no unique type (IBC-NST). There were 35 instances of invasive lobular cancers (ILC), 48 instances of breast cancers with medullary features, nine instances of mucinous cancers and eight instances of neuroendocrine cancers. The remaining 45 instances were of additional miscellaneous histologic types, including micropapillary carcinoma, papillary carcinoma, tubular carcinomas, tubulo-lobular carcinoma and metaplastic carcinomas. Details of the clinico-pathologic features are summarized in Table ?Table2.2. Overall, 418 instances (36.9%) were DCLK1 high and 513 instances (63.1%) were DCLK1 low. Representative staining is demonstrated in Figure ?Number11. Table 2 Correlation of DCLK1 manifestation with clinic-pathological features Number 1 Representative immunohistochemical staining of DCLK1 (x400) Correlation with clinico-pathologic features, biomarkers and molecular subtypes Large DCLK1 manifestation correlated with lower grade (< 0.001), the absence of FF (=0.045), the absence of necrosis (= 0.005), the absence of LVI (= 0.004) and reduce pN stage (= 0.002) but not age, EIC and pT stage (Table ?(Table22). Among the 1121 invasive cancers with complete IHC data for molecular subtypes classification, 536 (47.8%) were luminal A, 320 (28.5%) were luminal B, 112 (10.0%) were HER2-OE and 153 (13.7%) were triple negative breast cancers (TNBC) (including 68 (6.1%) BLBC and 85 (7.6%) unclassified). The DCLK1 expression rate was DIAPH1 47.2% in luminal A, 34.4% in luminal B, 22.3% in HER2-OE and 17.0% in TNBC (23.5% in BLBC and 11.8% in unclassified). DCLK1 expression showed a differential expression in different molecular subtypes with the highest prevalence in luminal cancers (< 0.001) (Table ?(Table22). In line with that, DCLK1 also correlated positively with the expression of ER and PR (< 0.001 for both). Additionally, DCLK1 correlated with expression of AR (= 0.010), SYN (< 0.001) and CG (<0.001) positively but negatively with HER2 (= 0.001), Ki67 (< 0.001), c-Kit (= 0.034), CK5/6 (= 0.030) and p-cadherin (< 0.001). There was no significant correlation with EGFR, p63, CK14, CD44, ALDH1, vimentin and SOX2 (Table ?(Table3).3). By multivariate analysis, only LVI (OR=0.590, = 0.001, 95% CI=0.427-0.817), ER (OR=2.316, < 0.001, 95% CI=1.648-3.255), CG (OR=1.611, = 0.019,95% CI=1.080-2.401) and SYN (OR=1.655, < 0.001,95% CI=1.298-2.110) were found to be independent parameters associated with DCLK1 expression (Supplementary Table S1). Similar results were obtained when DCLK1 expression was analyzed as a continuous variable, except for FF (Tables ?(Tables22-?-33 and Supplementary Table S2). Table 3.