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Figure 4 shows a representative pattern of Ki-67 and cyclin E SI in intermediate-risk mixed type tumors with (Fig. 4A,C,E and G) or without metastasis (Fig. 4B,D,F and H).
Exclusion of mixed type tumors was done to analyse only clearly distinct tumor entities.
Only patients with either intestinal (n = 59) or diffuse type tumors (n = 59) according to the Laurén classification were included for further analysis, mixed type tumors were excluded (n = 12).
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A much rarer variant of such mixed type tumor harbors teratoid features, which contains foci of mature cartilage, intestinal-type or keratinized epithelium, melanin pigment, or skeletal muscle in addition to the elements mentioned above.
We further classified the metabolic phenotypes of breast cancer as follows: Warburg type: tumor (glycolysis type), stroma (nonglycolysis type); reverse Warburg type: tumor (nonglycolysis type), stroma (glycolysis type); mixed type: tumor (glycolysis type), stroma (glycolysis); and null type: tumor (nonglycolysis type), stroma (non-glycolysis type).
Cases of adenomas, borderline tumors, and metastasis to the retroperitoneum were excluded, but mixed-type tumors were included.
Mixed-type tumors were categorized together with the diffuse type.
Moreover, the stratified analysis by Lauren's histological type revealed that patients with intestinal-type tumors, but not those with diffuse or mixed-type tumors, responded to immunotherapy.
A retrospective subgroup analysis of patients by Lauren's histological type showed that patients with diffuse or mixed-type tumors seemed not to benefit from adjuvant immunotherapy.
This may be an important reason why patients with diffuse and mixed-type tumors do not benefit from immunotherapy disease advances rapidly or patients die before immunotherapy can have an important effect.
Data from the 3,665 patients who were successfully screened by either IHC or FISH for this study confirm previous reports that HER2 overexpression or amplification is more common in patients with intestinal-type tumors compared with diffuse- or mixed-type tumors [ 5, 6].
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