title: IGF-I in human breast cancer: low differentiation stage is associated with decreased IGF-I content.
abstract: OBJECTIVE
  Few investigations on the potential role of IGF-I in human breast cancer have used morphological criteria, and the data presented on the localisation of IGF-I are controversial. Moreover, little information exists on a potential correlation between local IGF-I and the grade of malignancy or prognostic factors. Therefore, we investigated the immunohistochemical localisation of IGF-I in specimens of human breast cancer tumours of the ductal type, graded as G1/G2 (well-/moderately differentiated, n=115) and G3 (poorly differentiated, n=28).
  
  
  METHODS
  IGF-I immunoreactivity was quantified using a scaling from no (-) to numerous (+++) IGF-I-immunoreactive cells. From 29 of the G1/G2 and 17 of the G3 tumours IGF-I was also measured by RIA. Cytosolic oestrogen receptor (ER) and progesterone receptor (PR) levels, and S-phase fraction were established and related to the number of IGF-I-immunoreactive cells.
  
  
  RESULTS
  IGF-I immunoreactivity occurred predominantly in ductal epithelial cells. Of G3 tumours, 57% exhibited IGF-I immunoreactivity as compared with 84% of G1/G2 tumours. Correspondingly, the amount of IGF-I measured by RIA was significantly lower in G3 tumours (6.9+/-0.9 ng/g wet weight) than in G1/G2 tumours (10.5+/-1.1 ng/g wet weight) (P=0.031). G1/G2 tumours exhibited a higher percentage of IGF-I-immunoreactive cells (16% -, 23% +, 41% ++, 20% +++) than G3 tumours (43% -, 37% +, 12% ++, 8% +++). When comparing the - with the +++ G1/G2 tumours, the frequency of IGF-I-immunoreactive cells was related significantly to the ER (P<0.016) and the PR (P<0.008) levels. In G1/G2 and G3 tumours, the ER and PR levels increased with the amount of IGF immunoreactivity while the S-phase fraction increased with decreasing IGF-I content. In 25% of the specimens, IGF-I immunoreactivity occurred in stromal cells, but there was no obvious difference between the different types of tumours. The survival of the G1/G2 tumour patients increased with increasing numbers of IGF-I-immunoreactive cells.
  
  
  CONCLUSIONS
  It is concluded that IGF-I is associated with the more-differentiated type of epithelial cells and that increasing dedifferentiation goes along with decreased IGF-I content. Thus, the presence of IGF-I immunoreactivity in breast cancer epithelial cells indicates a lower degree of malignancy than the lack of IGF-I.
authors.affiliation: Institute of Anatomy, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Eppler
authors.forename: J
authors.initials: J
authors.lastname: Zapf
authors.forename: N
authors.initials: N
authors.lastname: Bailer
authors.forename: U G
authors.initials: UG
authors.lastname: Falkmer
authors.forename: S
authors.initials: S
authors.lastname: Falkmer
authors.forename: M
authors.initials: M
authors.lastname: Reinecke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000276:immunology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011863:Radioimmunoassay; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016196:S Phase
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D007334:Insulin-Like Growth Factor I