title: In phyllodes tumour of the breast expression of c-kit but not of ALDH1A1 is associated with adverse clinico-pathological features.
abstract: Attempts at identification of an ideal prognostic/predictive biomarker in phyllodes tumour (PT) have not been fruitful so far. Studies evaluating c-kit expression in PT have shown contradictory results. Recently aldehyde dehydrogenase 1A1 (ALDH1A1) was proposed as a stem cell marker for malignant PT but its expression has not been studied in benign and borderline tumours. We aimed to evaluate expression and prognostic significance of c-kit and ALDH1A1 in different grades of PT. Epithelial and stromal c-kit and ALDH1A1 expression were studied in 104 PT cases (86 primary and 18 recurrent tumours) and compared with different clinico-pathological features and recurrence rates. Stromal c-kit expression at 1 % cutoff correlated with increasing tumour grade, larger tumour size, hypercellularity, nuclear atypia, stromal overgrowth, infiltrative margins and mitotic count. These associations, however, were lost with higher (5 or 10 %) cutoffs. Conversely, decreased c-kit expression in the epithelial component correlated with increasing tumour grade, regardless of the cutoffs used. Stromal ALDH1A1 expression did not have significant associations with tumour grade or other adverse clinico-pathological features, regardless of different cutoffs. None of the cases showed significant epithelial ALDH1A1 expression. Expression of c-kit was associated with poorer overall survival (p = 0.011), while ALDH1A1 expression was associated with shorter recurrence-free survival (p = 0.036). In conclusion, c-kit expression was associated with higher tumour grade and adverse clinico-pathological features. However, these associations are cutoff dependent, partly explaining the variability in previously reported studies. ALDH1A1 expression did not have significant correlations with tumour grade and adverse clinico-pathological variables.
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chougule
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India. docaman5@hotmail.com.
authors.forename: Amanjit
authors.initials: A
authors.lastname: Bal
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India.
authors.forename: Ashim
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of General Surgery, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India.
authors.forename: Pavneet Singh
authors.initials: PS
authors.lastname: Kohli
authors.affiliation: Department of General Surgery, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India.
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000032:analysis; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D003557:Phyllodes Tumor / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012008:Recurrence; D050697:Retinal Dehydrogenase; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D019009:Proto-Oncogene Proteins c-kit
keywords: ALDH1A1; Breast; C-kit; Phyllodes tumour; Recurrence