Table 1.
Histological feature of the study set.
Table 2.
Histological grading and morphology of BC patients.
Fig 1.
Example of the histologic classification of G1 (A), G2 (B) and G3 (C) as well as LG (D) and HG (E) BCs among study cases (original magnification x20).
Table 3.
Distribution of TP53 and FGFR3 somatic mutations in LG and HG tumors.
Table 4.
Distribution of TP53 and FGFR3 somatic mutations in relation to tumor morphology and histology.
Table 5.
Detailed distribution of TP53 somatic mutations in LG and HG BCs.
Table 6.
Detailed distribution of FGFR3 somatic mutations in LG and HG BCs.
Fig 2.
Differential gene expression analysis between HG and LG tumors.
Survivin (A), CK20 (B), E-Cadherin (C) and CD44 (D) gene expression levels in LG and HG BCs. LG: Low Grade; HG: High Grade. Standard error of the mean (SEM) is indicated by the bars. n indicates the number of analyzed samples. * indicates p-value <0.05.
Fig 3.
Differential gene expression of CK20, CD44, E-cadherin, and Survivin in relation to FGFR3 and TP53 mutational status of LG and HG BCs.
CK20, E-cadherin, CD44 and Survivin mRNA levels in TP53-FGFR3 wild type, FGFR3 mutated, TP53 mutated and FGFR3-TP53 mutated LG tumors (A). CK20, E-cadherin, CD44 and Survivin in TP53-FGFR3 wild type, FGFR3 mutated and TP53 mutated HG tumors (B). Only one HG tumor showed overlapped TP53-FGFR3 mutations. It is no sufficient for any statistical analysis. CK20: cytokeratin 20; E-CAD: E-cadherin: Low Grade; HG: High Grade. Standard error of the mean (SEM) is indicated by the bars. n indicates the number of analyzed samples. * indicates p-value <0.05.
Fig 4.
Intergene multivariable analysis.
Multivariable analysis of CD44, CK20, E-cadherin (ECAD) and Survivin in all BCs, HG and LG BCs taking in account also the mutational status of both TP53 and FGFR3 genes. To underline the statistically significant correlations, p-value is reported in red. (StatGraphics XVI software).
Fig 5.
Differential gene expression analysis within tumor grading.
Survivin (A), CK20 (B), E-cadherin (C) and CD44 (D) gene expression levels in G1, G2 and G3 BCs. G1: Grade 1; G2: Grade 2; G3: Grade 3. Standard error of the mean (SEM) is indicated by the bars. n indicates the number of analyzed samples. * indicates p value < 0.05.
Fig 6.
Differential gene expression analysis within BC morphology.
Survivin (A), CK20 (B), E-cadherin (C) and CD44 (D) gene expression levels in the BCs subtypes defined by the BC morphology. G1+G2 were LG with papillary morphology; papillary G3 were HG characterized as papillary protrusion; flat G3 were HG with non papillary morphology. Standard error of the mean (SEM) has indicated by the bars. n indicates the number of analyzed samples. * indicates p value < 0.05.
Fig 7.
Unsupervised clustering analysis combining gene expression levels of CK20, CD44, E-CAD and Survivin genes created 4 distinct clusters (A). Gene expression levels of CK20, CD44, E-CAD and Survivin genes in the clustering of BCs defined by their grading and morphology (B). It is possible to identify similar trends in gene expression profile between Cluster 2 and G2 group and Cluster 4 and G3 non papillary (G3 flat) group.
Fig 8.
Histotype distribution in clusters.
Unsupervised clustering analysis performed on gene expression values of CD44, E-cadherin, Survivin and CK20 in BCs revealed specific BC histotype distribution within clusters. LG: low grade; HG: high grade.
Table 7.
Distribution of BC samples within clusters (1–4).