Table 1.

The histopathology of CD44 in breast cancer

ReferencesBenign or noninvasiveInvasive and node-negativeInvasive and node-positiveIsoforms examinedCorrelations and conclusionsCD44 association
Joensuu et al. (101)No noninvasive tumors were evaluated.Evaluated 106 node-negative invasive carcinomas.Evaluated 75 node-positive carcinomasExamined CD44s expression.Sixteen percent of thetumors examined had >90% positive expression for CD44s, and those tumors that were >90% CD44-positive were more often poorly differentiated, had higher mitotic counts, and were often ER-negative.Unfavorable
Kaufmann et al. (64)Three tumors withlow histological grade.Thirty-three lymphnode–negative tumors; local invasion not reported.Evaluated 100 primaryinvasive tumors, 12 local recurrences, and 18 lymph node metastases.Examined CD44v3, v5, and v6.CD44v6 was expressedin 84% of primary tumors and 100% of metastases and recurrences. CD44v6 expression correlated with poor OS. There was no correlation between other variants and OS.Unfavorable
Friedrichs et al. (97)Evaluated 108 node-negative samples by IHC.Not reported.119 node-positivepatients by IHC and 43 high-risk cases by RT-PCR. Follow-up 7 years.Examined CD44s, v4, v6, and v9.No significantcorrelations between CD44s and CD44v9 with DFS or OS were observed, but they were more often expressed in lower pathological grade tumors. CD44v6 was associated with less aggressive tumors but did not correlate with OS or DFS.Favorable
Diaz et al. (95)NAEvaluated 230 lymphnode–negative invasive tumors. Mean follow-up of 15 years.NAExamined CD44s and CD44v6.High CD44s expressionwas correlated with increased DFS. CD44v6 expression was not associated with clinical outcomes.Favorable
Jansen et al. (98)Evaluated 183 lymphnode–negative samples.Evaluated 136 node-positive samples. Mean follow-up of 128 months.Examined CD44v6.CD44v6 expressioncorrelated with smaller tumor size and lymph node–negative status.Favorable
Tokue et al. (99)Examined breast tumors from 95 patients by RT-PCR and IHC. Did not mention tumor grade or invasive status.Examined CD44v6 and CD44v2.CD44v6 was expressed in 73% of tumors, and CD44v2 was expressed in 35% of tumors. CD44v6 expression was correlated with OS, whereas v2 expression was correlated with reduced OS.Dependent on variant expression.
Bànkfalvi et al. (100)Evaluated 152 breast carcinomas, including 20 DCIS and 19 LCIS.Did not report lymph node status.Evaluated 152 breast carcinomas, including 56 IDC and 17 ILC. Mean follow-up was 72 months.Examined CD44v3, v4, v6, v7 and v9.The loss of CD44v6expression correlated with poorly differentiated tumors (grades 3 and 4) but was associated with favorable overall survival. Expression of CD44v4 and v7 correlated with lymph node–positive status, but it did not correlate with patient survival.Dependent on variant expression.
Foekens et al. (96)Evaluated 72\noninvasive tumors.Evaluated 165 node-negative invasive cases.Evaluated 230 node-positive primary cases.Examined CD44v6, v7/9, v9, and v10.CD44v6 expression wasassociated with a favorable prognosis in node-negative patients. The other variants were not significantly associated with relapse-free survival.Favorable
Bànkfalvi et al. (93)Evaluated 142 breast carcinomas, including 19 DCIS and 9 LCIS.Did not report lymph node status.Evaluated 142 breastcarcinomas, including 44 IDC and 17 ILC. Mean follow-up was 72 months.Examined CD44v4,v6, and v7.Lack of CD44v6 expression correlated with poor survival.Favorable
Berner et al. (104)Evaluated 59 pleural and peritoneal effusions, including benign effusions.NAEffusions including malignant or atypical cells.Examined CD44s andCD44v3–10.CD44s expression waspositive in 94% of benign cells and 23% of malignant or atypical cells. CD44v3–10 was positive in 6% of benign cells and 55% of malignant or atypical cells. Expression of variants was higher in breast cancer than in corresponding normal cells.Neutral
Morris et al. (105)Evaluated 109 patients with stage 2 cancer, with a minimum 5-year follow-up, but did not differentiate between size and lymph node status.Examined CD44s and CD44v6.CD44s was detected in26% of tumors and v6 was detected in 80% of tumors, independently of lymph node status. No association was observed between CD44s or v6 expression with DFS or OS.Neutral
Berner et al. (94)Evaluated 40 node-negative tumors, including histological grades 1–3.N/AEvaluated 68 node-positive tumors. Mean follow-up time was 67 months.Examined CD44s, v5,v6, v7, and v3–10.Increased CD44smRNA correlated with lower pathological grade, DFS, and OS. CD44s and v6 mRNA correlated with lower pathological grade. The other variants did not correlate with histological subtype, OS, or DFS.Favorable
Auvinen et al. (103)Evaluated 15 benignand 6 premalignant breast tumors.Evaluated 30 cases of IDC, 12 cases of LDC, and 12 other invasive breast tumors.Examined CD44s, v3, and v6.CD44s and v3 werelowly expressed in benign or premalignant tumors, and v6 was expressed in 20–30% of ductal epithelium. CD44s, v3, and v6 were upregulated in invasive carcinomas, but the authors reported no correlation with DFS or OS.Not assessed for clinical outcome.
Yu et al. (102)None evaluated.Evaluated 60 invasive node-negative carcinomas.Evaluated 38 node-positive invasive ductal carcinomas.Examined CD44v6and found 38.8% of samples positive for CD44v6 expression.CD44v6-positive cellscorrelated with shorter DFS and OS, and they were an independent biological marker for prognosis.Unfavorable
Brown et al. (91)Evaluated 5 normal samples and breast tumors graded 1.Evaluated 27 tumors, including grades 2 and 3.Examined CD44s and CD44v5, v6.CD44s did not differ between normal breast tissue and grade 1 tumors. CD44s was highly elevated in grades 2 and 3 tumors. CD44v5 and v6 expression did not differ between tumor grades.Unfavorable

Abbreviations: DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma; LCIS, lobular carcinoma in situ; LDC, lobular invasive carcinoma.