MET expression is associated with disease-specific survival in breast cancer patients in the neoadjuvant setting

MET and RON receptor tyrosine kinases play an important role in tumor progression. The aim of this study was to determine the predictive or prognostic impact of MET and RON in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Immunohistochemical analyses were performed to retrospectively examine the predictive or prognostic impact of MET and RON expression in 129 breast cancer patients treated with NAC followed by definitive surgical resection. MET-positive tumors were detected in 89 patients (68.9%) and RON-positive tumors in 94 patients (72.9%). Survival analysis showed that MET expression was correlated with longer disease-specific survival (DSS; P = 0.016), whereas RON expression was not associated with survival rates. MET expression was a significant factor for DSS in the non-pCR group in subgroup analysis (P = 0.024) and a marginal significant independent prognostic factor for DSS in multivariate analysis. The MET-positive group had higher pCR than the MET-negative group but the difference was not statistically significant (P = 0.266). MET expression is a prognostic factor for DSS in breast cancer patients receiving NAC and may provide additional prognostic information in patients not achieving a pCR.     

Prognostic importance of PAI-1 in node negative breast cancer patients--results after 10 years of follow up

The serine protease urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play key roles in the proteolytic cascade involved in physiological and pathological degradation of the extracellular matrix.The aim of this study was to determine the prognostic importance of PAI-1 expression in tumor cells in node-negative breast cancer patients that did not receive adjuvant chemotherapy. We used immunohistochemistry (IHC) as a detection method. The study retrospectively included 133 ductal invasive breast cancer patients from the Clinical Hospital Center Zagreb, Croatia, surgically treated in a two-year interval (1998-1999) with 10 years of follow up.The Cox proportional hazard regression test with stepwise variable selection was used to calculate the relative effect of investigated data on patients’ prognosis. Univariate analysis showed that all investigated factors, such as lymph node involvement (p = 0.025), tumor grade (p < 0.001), estrogen receptor status (p = 0.011), vascular invasion (p = 0.001), HER2 overexpression (p < 0.001), and proliferative index (p < 0.001), had a statistically significant influence on patients’ OS. Multivariate statistical analysis showed that only HER-2 (p < 0.001) can be considered an independent, statistically significant poor prognostic factor.In patients with negative lymph nodes that did not receive adjuvant chemotherapy, we found a significant correlation in overall survival (p = 0.009), which is favorable for PAI-1 negative tumors.In conclusion, it seems that PAI-1 in primary breast cancer tissue correlates with disease aggressiveness and has a strong prognostic impact on primary breast cancer, and is a strong prognostic factor for node-negative patients that did not receive chemotherapy.     

Prognostic significance of p16INK4a/p53 in Tunisian patients with breast carcinoma

Infiltrating ductal carcinoma (IDC) of the breast is a result of genetic alterations that affect the regulation of the cell cycle check-point and apoptosis. The aim of the present study was analysis using immunohistochemical localization of mouse double minute-2 (mdm2), p16INK4a, p53, bax and bcl-2 markers in Tunisian patients with breast IDC and to determine if there was correlation with the major clinico-pathological parameters and with survival of patients. We showed that the expression of p53, p16INK4a, mdm2, bcl-2, and bax was observed in 46.3%, 20.7%, 38%, 50% and 11.9% of cases, respectively. Statistical analysis revealed that positive expression of mdm2 was associated with larger tumors (P = 0.013), whereas bax positivity was more prevalent in younger patients and in tumors of smaller size (P = 0.008 and P = 0.012 respectively). Furthermore, the expression of p16INK4a correlated with advanced grade (P < 0.0001), triple negative tumors (ER-/PR-/HER2-, P = 0.001) and mdm2 expression (P = 0.017). The absence of nuclear p53 accumulation was predictive of good prognosis as well as when it was associated with negative expression of p16INK4a. Our findings suggest that among the biomarkers tested, p16INK4a might have a useful clinical and prognostic significance in infiltrating ductal carcinoma of the breast.     

Effect of BRCA1 immunohistochemical localizations on prognosis of patients with sporadic breast carcinomas

Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67. BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells. Nuclear BRCA1 immunoreactivity showed no relation with the classic clinicopathological markers and the expression of cerbB2, p53 and Ki67. Reduced expression of nuclear BRCA1 protein was found to exert an independent favorable impact on both the overall and relapse-free (RF) survival of the patients (p = 0.019 and p = 0.043, respectively). Cytoplasmic BRCA1 was associated with none of the classic histomorphological indices, except from the lymph node metastasis, with which its relation was found to be inverse (p = 0.05), prolonging the RF survival of the patients (p = 0.05). Our findings suggest that BRCA1 protein depicts different prognostic significance, according to its subcellular distribution. Nuclear detection of the protein was associated with a worse prognosis, while the cytoplasmic one was related to fewer recurrences as a result of fewer lymph node metastases.     

Downregulation of GLTSCR2 expression is correlated with breast cancer progression

Glioma tumor-suppressor candidate region gene2 (GLTSCR2) is a recently identified nucleolus-localized protein participating in the regulation of cell cycle progression and apoptosis. Down-regulation of GLTSCR2 in several types of cancers and increased transforming activity in GLTSCR2-downregulated cancer cells indicated its tumor suppressive potential. The aim of this study was to evaluate GLTSCR2 expression in breast cancer and to investigate the question of whether reduced expression of GLTSCR2 may have any pathological significance in breast cancer development or progression. In this study, we performed quantitative RT-PCR and immunohistochemistry to evaluate the expression of GLTSCR2 and relevance with clinicopathological factors in the invasive ductal carcinoma (IDC). GLTSCR2 expression was reduced in 48% of IDC (n = 426) by a semi-quantitative scoring system using tissue microarray. GLTSCR2 mRNA was significantly reduced by 0.16 fold in 15 out of 17 (88%) cases of IDC. Reduction of GLTSCR2 was significantly correlated with increased histological grade (p < 0.005), increased tumor size (p < 0.001), axillary lymph node involvement (p < 0.001) and decreased disease free survival (p < 0.025). In addition, we show that upregulation of GLTSCR2 decreases the invasive potential of breast cancer cells. Taken together, our data suggest that GLTCR2 may play a role in the tumorigenesis, progression and biological behavior in breast cancer.     

Evaluation of O6-methylguanine-DNA methyltransferase by immunohistochemistry: Best clinical and research practices

O6-Methyguanine-DNA methyltransferase (MGMT) repairs DNA damage and acts as a tumor suppressor in normal cells by preventing DNA mutations. Several antibodies against MGMT are used for immunohistochemical assessment of this marker and no universal standard is adopted.We evaluated the immunohistochemical expression of MGMT with 5 commercially available primary antibodies in 59 invasive breast carcinomas.A tissue microarray was constructed using 59 invasive breast carcinoma samples. Five primary antibodies against MGMT were used for immunohistochemistry, including clones MT3.1, SPM287, and MT23.2. Heat-induced antigen retrieval and polymer-based immunohistochemistry were performed. Stains were analyzed by microscopy and automated digital slide technology. qRT-PCR was performed for all tumors.Clone SPM287 had the highest sensitivity (p < 0.001), and clone MT3.1 had the lowest sensitivity (p < 0.001). Clone MT23.2 generated higher levels of cytoplasmic staining, which was not observed with the other antibodies (p < 0.001). Fifty-six samples (94.9%) showed hypoexpression of MGMT compared with normal breast, as measured by qRT-PCR (p < 0.001). Only clone SPM287 correlated significantly with the qRT-PCR results (p = 0.027).Antibody clone SPM287 is the most sensitive and specific antibody for the immunohistochemical evaluation of MGMT, rendering it a reliable and effective reagent for research and clinical practice in breast cancer.     

An immunohistochemical study of interleukin-8 (IL-8) in breast cancer

The use of prognostic markers for breast cancer is important for routine diagnosis and research. Interleukin-8 is a chemotactic cytokine produced by several cell types in response to inflammation, however, its expression, regulation and function are poorly understood. Recent studies have associated angiogenesis and inflammatory processes with tumor malignancy. The present study investigated the correlation between interleukin-8 expression and breast cancer prognosis. Interleukin-8 expression was assessed in 72 women with mammary neoplasia by immunohistochemistry and the results were statistically correlated with clinical-pathological findings. There was an inverse correlation between interleukin-8 expression and metastasis (p = 0.03) and/or local recurrence (p = 0.02). In the patient group that received post-surgery chemotherapy and radiotherapy, a lower interleukin-8 expression was found in those women that showed local recurrence (p = 0.01). Multivariate logistic regression showed estrogen receptor negativity, progesterone positivity and metastasis with increased risk of death (p < 0.05). The data reflect the complexity of the role of interleukin-8 in tumor microenvironment and support its classification as a possible prognostic marker, although more studies are necessary for its inclusion in clinical practice.     

Clinicopathologic correlation of cancer stem cell markers CD44, CD24, VEGF and HIF-1α in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study

CD24^−/lowCD44⁺ cells have been identified as putative cancer stem cells (CSCs) in breast cancer. However, the expression of these markers, as well as their association with clinical parameters or tumor microenvironment of breast cancer, remains largely unknown. In the present study, we examined the expression of CD44, CD24, VEGF, and HIF-1α in human breast tumor tissues and assessed their clinicopathological correlations. We investigated tissue samples, including 117 cases of invasive ductal carcinoma (IDCa), 14 cases of ductal carcinoma in situ (DCIS), and 15 cases of intraductal hyperplasia (IDH) from breast tissues. The expression of CD44, CD24, HIF-1α, and VEGF was evaluated using immunohistochemical staining. CD24, CD44, HIF-1α, and VEGF were expressed in 49 (41.9%), 51 (43.6%), 32 (27.4%), and 97 cases (82.9%), respectively, in IDCa. CD24^−/lowCD44⁺ cells were noted in 48 (41.3%) cases. The levels of CD24 and VEGF expression correlated positively with tumor malignancy (P < 0.05). Meanwhile, the expression of CD24, CD44, and VEGF correlated significantly positively with increasing tumor grade (P < 0.05). In addition, associations between CD44 and VEGF, CD24 and VEGF, HIF-1α and VEGF, CD24^−/lowCD44⁺ and VEGF, CD24^−/lowCD44⁺ and HIF-1α were also observed (P < 0.05). The HIF-1α expression level was relatively higher in early stage breast cancer patients with CD24^−/lowCD44⁺ cells. Taken together, our results suggest that CD24 and VEGF may play important roles in breast tumorigenesis and progression, while HIF-1α may play a role in the early stage of breast carcinogenesis.     

Decreased HCRP1 expression is associated with poor prognosis in breast cancer patients

Background: Downregulation of hepatocellular carcinoma related protein 1 (HCRP1) has been reported to be associated with a poor prognosis in a variety of malignant tumors. The purpose of this study was to assess HCRP1 expression in breast cancer and to examine its possible correlation with commonly used prognostic factors, particularly epidermal growth factor receptor (EGFR). Methods: Immunohistochemical analysis was performed on tumors from 194 patients with primary breast cancer. HCRP1 expression was analyzed along with major clinicopathological variables. Results: HCRP1 protein expression was shown to be correlated with age (P = 0.001), histological grade (P = 0.005), tumor progression (P = 0.013), and death (P = 0.001), but not with tumor size, lymph-node metastasis, or Ki67 status. Kaplan-Meier survival curves showed that lower HCRP1 expression was significantly correlated with increased short-term survival (P < 0.001), and both univariate and multivariate analyses revealed that HCRP1, tumor size, lymph-node metastasis, and human epidermal growth factor receptor-2 (HER-2) were independent prognostic factors (all P < 0.05). In addition, low HCRP1 expression was much more frequent in triple negative breast cancer (TNBC; 63.89%) than in luminal (16.95%) and HER-2 overexpression phenotypes (7.5%; P < 0.001), and significant correlations between HCRP1 and survival time were observed for the TNBC group (P < 0.004). Furthermore, an inverse relationship between HCRP1 and EGFR expression was found both for the complete set of all cases (P < 0.001), and for each phenotype analyzed individually (P < 0.05). Conclusion: Our results suggest that HCRP1 may play an important role in EGFR regulation and that its decreased expression is an independent predictor of breast cancer, especially in TNBC patients.     

Investigation of Epstein-Barr virus in breast carcinomas in Tunisia

Breast carcinoma is a major cause of death among women, and the potential implication of viruses in its pathogenesis remains worth a hypothesis. The potential role of Epstein-Barr virus (EBV) in its pathogenesis is still a subject of continued discussion and investigation. The aim of this study was to evaluate the prevalence of EBV in sporadic breast cancers in Tunisia, and to determine the clinicopathological characteristics of virus-positive cases. Viral presence has been evaluated by polymerase chain reaction (PCR), in situ hybridization, and immunohistochemistry investigated on tumor tissues and their corresponding normal breast tissues collected from 123 Tunisian women with sporadic breast carcinomas. Viral status in tumors was then correlated with various clinicopathological parameters.Using specific PCR assays, EBV DNA was found in 33 (27%) out of 123 breast carcinoma cases. EBV-encoded small RNAs (EBERs) in situ hybridization was negative in the neoplastic cells, but stomal lymphocytes were positive in 4 cases. Immunohistochemistry for latent membrane protein 1 (LMP1) was negative in all cases. None of the normal breast tissues showed positive results for EBV using PCR, in situ hybridization, and immunohistochemistry.A correlation was found between EBV DNA presence and the negativity of estrogen receptor (P = 0.008). However, no significant correlation was found for the other parameters investigated, including patient age, Scarff-Bloom-Richardson (SBR) histological grade, tumor size, and histological node involvement.With regard to survival data, overall and disease-free survivals were shorter in EBV-positive breast carcinoma cases than in EBV-negative ones, but this difference did not reach statistical significance.Our study indicates the presence of EBV DNA in a significant proportion of breast cancer in Tunisia. Further studies are required to elucidate the role of this virus in breast carcinogenesis.     

Prognostic factors in patients with metastatic breast cancer at the time of diagnosis

Approximately 90% of breast cancer mortality is due to metastases that are resistant to adjuvant therapies. Thus, assessment of factors associated with clinical outcomes in patients with advanced breast cancer is of significant importance. Despite the recent improvement in early detection, between 5 and 10% of breast cancer patients are diagnosed with metastasis at initial presentation or, rarely, before the primary breast cancer has been identified. These patients typically have poorer survival outcomes compared to those who develop distant metastasis subsequently. Yet, the prognostic relevance in these patients has not been intensively explored. In this study, we analyzed breast cancer patients with distant metastasis at the time of diagnosis between 1997 and 2010 (n = 194) to identify the clinicopathological factors significant for overall survival. By univariate analysis, race, estrogen receptor (ER) and progesterone receptor status were significantly associated with overall survival, while race and ER remained independent factors in multivariate analysis. Being Caucasian and overexpressing of ER both showed a significantly decreased hazard of death (P = 0.015 and 0.017, respectively). Reflecting these findings, the overall survival differed significantly between breast subtypes, with the luminal subtype and triple negative disease being associated with the longest and worst survival, respectively. Further, multi-organ involvement was associated with a worse prognosis than those with single organ metastasis, whereas no significant difference in survival was found between the different anatomic sites (bone, viscera and brain). Our findings suggest that it is predominantly the intrinsic nature of the tumor along with the genetic makeup of the patient that predicts the prognostic outcome in those patients with advanced disease at presentation.     

The expression of ERCC1, RRM1, and BRCA1 in breast cancer according to the immunohistochemical phenotypes

We studied the expression of BRCA1, ERCC1, and RRM1 which play an important role in DNA repair systems in breast cancer. Immunohistochemical staining for EGFR, BRCA1, ERCC1, and RRM1 were performed by using a tissue microarray made from 230 breast cancer patients. Patients were classified into luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) types according to ER, PR, and HER-2 expression. The expression of ERCC1, RRM1, and BRCA1 were correlated (P < 0.05). The expression level of ERCC1 was the lowest in TNBC type (P = 0.031), ERCC1 negativity was more prominent in TNBC and luminal B groups than luminal A and HER-2 groups (P = 0.013). Cases with EGFR overexpression showed high expression of RRM1 and BRCA1 (P = 0.046, and 0.004, respectively). In conclusion, the expression of ERCC1 is particularly lower in TNBCs than other types of breast cancers.     

Immunohistochemical COX-2 overexpression correlates with HER-2/neu overexpression in invasive breast carcinomas: a pilot study

Cyclooxygenase-2 (COX-2) is a prostaglandin synthase that catalyzes the synthesis of prostaglandin G2 and H2. It has been shown that COX-2 plays an important role in tumorigenesis of different tumor types and it is thought to take part in breast carcinogenesis. In the present study, we aimed to investigate the relationship of immunohistochemical COX-2 expression with clinicopathological parameters, including HER-2/neu overexpression in invasive breast carcinoma (IBC).Our study population comprised 10 normal breasts, 25 ductal carcinomas in situ (DCIS), and 51 invasive breast carcinomas. Immunohistochemical overexpressions of COX-2 and HER-2/neu were investigated in sections of formalin-fixed, paraffin-embedded blocks by 3 observers.In normal breast, DCIS and IBC, the COX-2 overexpression rate was 0%, 84%, and 58.8%, respectively. In IBC, COX-2 overexpression had a significant relationship with HER-2/neu overexpression (p = 0.026) and a high histological grade (p = 0.026). COX-2 expression in both DCIS (n = 25) and IBC (n = 51) was significantly higher than in normal breast tissue (p < 0.0001). In addition, the COX-2 expression rate was significantly higher in DCIS than in IBC (p = 0.042).Our results indicated that COX-2 overexpression correlates with aggressive phenotypic features, such as HER-2/neu overexpression and high histological grade in IBC. Increased expression of COX-2 in both DCIS and IBC in comparison to normal breast could indicate a role in breast carcinogenesis. COX-2 overexpression may provide a clinically useful biomarker for estimating tumor aggressiveness.     

ERCC1 expression and tumor regression predict survival in esophageal squamous cell carcinoma patients receiving combined trimodality therapy

Purpose

Combined trimodality therapy with neoadjuvant chemoradiation followed by surgery has shown promising results for locally advanced operable esophageal cancer. DNA repair proteins may affect treatment efficacy through repairing DNA damage induced by chemotherapy and radiation therapy. We evaluated the associations of XRCC1, ERCC1 and MGMT expression with histopathologic response and survival in patients with locally advanced operable esophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiation.

Methods

Paraffin-embedded pre-treatment tissue samples, collected by endoscopic biopsy from patients treated with cisplatin-based neoadjuvant chemoradiation followed by surgery, were immunohistochemically stained for XRCC1, ERCC1 and MGMT expression.

Results

Of the 44 patients, major histopathologic response was noted in 26 (59.1%) patients. 68.8% of patients with ERCC1-negative tumors had major histopathologic response, compared to 53.6% of those who expressed positive ERCC1, though the difference was not statistically significant (P = 0.361). The patients with ERCC1-negative tumor presented much better overall survival than those positive for ERCC1 expression (P = 0.018). Patients with major histopathologic response had a 3-year survival rate of 96.2% versus those with minor response, with a 3-year survival rate of 41.5% (P = 0.000). Multivariate analysis showed that ERCC1 expression and histopathologic response were independent predictive factors of overall survival in patients with locally advanced operable ESCC receiving neoadjuvant chemoradiation.

Conclusion

Patients with ERCC1-negative tumors show a benefit from neoadjuvant chemoradiation, ERCC1 expression and tumor regression are useful predictive markers in patients with locally advanced operable ESCC receiving neoadjuvant chemoradiation followed by surgery.     

Serum tissue polypeptide-specific antigen is an independent predictor in breast cancer

Tissue polypeptide-specific antigen (TPS) is a tumor proliferative marker associated with cytokeratin 18. The aim of the study was to investigate the potential relationship between the preoperative serum TPS levels and the outcome in Chinese breast cancer patients. 975 consecutive female patients, affected by invasive breast cancer under investigation from January 2005 to December 2011, had their TPS levels measured with a one-step solid phase radiometric sandwich assay detecting the M3 epitope on cytokeratin 18 fragments. The cut-off value was 80 U/L. The average age diagnosed with breast cancer was 48, ranging from 23 to 71. About 19% (185) patients displayed an elevated preoperative TPS level (>80 U/L) associated with older age (>45), advanced cancer stage, larger tumor size (>2 cm), axillary lymph node metastasis, negative progesterone receptor status, and positive HER2 status. In addition, preoperative TPS levels were also significantly connected with recurrence (p < 0.05), particularly distant metastasis and visceral metastasis. The mean preoperative TPS level was 68.4 ± 116.43 U/L (range 0–1839 U/L). In multivariate analysis, high preoperative TPS level was recognized as an independent prognostic factor for disease-free survival (p < 0.001 and overall survival (p = 0.023). From these results we conclude that the serum preoperative TPS level may be a valuable and independent marker for breast cancer.     

High expression of integrin-linked kinase predicts aggressiveness and poor prognosis in patients with gastric cancer

Integrin-linked kinase (ILK), an intracellular serine/threonine protein kinase, has been reported to be highly expressed in many human malignancies, including gastric cancer. However, the prognostic significance of ILK expression in gastric cancer remains to be elucidated. In the present study, ILK expression in 95 gastric tumor tissues and 30 adjacent non-cancerous gastric mucosa was evaluated by immunohistochemistry and correlated with clinicopathological characteristics and patients’ outcome. The results showed that high ILK expression was observed in 47.4% (45/95) of gastric cancer tissues, but only in 20.0% (6/30) of adjacent gastric mucosa. Clinicopathological analysis indicated that high ILK expression was significantly associated with poor tumor differentiation (P = 0.024), advanced TNM stage (P = 0.006), tumor invasion (P = 0.001), and lymph node metastasis (P = 0.014). Kaplan–Meier survival curves demonstrated that patients with high ILK expression had substantially shorter overall survival that those with low ILK expression (P = 0.043, log-rank test). Furthermore, Cox multivariate regression analysis identified ILK expression as an independent prognostic factor for overall survival of gastric cancer patients (hazard ratio, 1.95; 95% confidence interval, 1.02–3.13; P = 0.026). In conclusion, our data suggest that ILK may contribute to the malignant progression of gastric cancer and serve as a novel prognostic indicator for gastric cancer patients.     

Aldehyde dehydrogenase 1 expression predicts poor prognosis in triple-negative breast cancer

Ohi Y, Umekita Y, Yoshioka T, Souda M, Rai Y, Sagara Y, Sagara Y, Sagara Y & Tanimoto A
(2011) Histopathology 59 , 776–780 Aldehyde dehydrogenase 1 expression predicts poor prognosis in triple‐negative breast cancer Aims: Aldehyde dehydrogenase 1 (ALDH1) has been identified as a reliable marker of breast cancer stem cells, and its clinical significance as a prognostic indicator of breast cancer has been reported by several investigators. However, the clinical significance of ALDH1 expression in triple‐negative (TN) breast cancer, a high‐risk breast cancer lacking the benefit of specific therapy, remains to be solved. Methods and results: We performed immunohistochemical analyses of 106 TN breast cancers, using paraffin‐embedded sections. The basal‐like phenotype was also investigated with the use of basal cytokeratin 5/6 and epidermal growth factor receptor. ALDH1 expression in carcinoma cells was found in 59% of cases and was correlated with high histological grade alone (P < 0.006), whereas ALDH1 expression in stromal cells was found in 49% of cases but was not correlated with any clinicopathological parameter. Patients with ALDH1 expression in carcinoma cells had a shorter relapse‐free survival (RFS) according to the log‐rank test (P = 0.015). According to Cox multivariate analysis, ALDH1 expression in carcinoma cells was an independent prognostic indicator of RFS (P = 0.025). The log‐rank test revealed that stromal expression of ALDH1 had no effect on RFS. Conclusions: ALDH1 expression in carcinoma cells is an independent prognostic factor in TN breast cancer patients.     

Three molecular classifications surrogate to four immunohistochemical markers in 374 invasive breast carcinomas with long follow-up: Which is better?

In the early 21st century, a new way to classify breast cancer appeared, based on their gene expression profiles. Various classifications have been proposed in an attempt to subrogate these molecular groups to an immunohistochemical expression of estrogen and progesterone receptors, HER2 and Ki67. We compared the three major molecular classifications (MCs) of 374 infiltrating breast carcinomas with the assumption that one is better than the others to discriminate the prognosis of patients that are classified by it. We found that [1] there was a significant statistical association with tumor grade and presence of associated HG-DCIS, but with differences in kappa indices [2]; MC3 showed a significant relationship with pathological tumor stage (p = 0.012, CI95% of 0.012–0.017); [3] only MC3 showed convincingly that the observed differences in OS were not due to chance in the univariate analysis (p = 0.04); [4] only MC3 is an independent prognostic factor of OS. In conclusion, these three classifications are not interchangeable; MC3, the only one that includes Ki67 expression in their defining criteria, is better in predicting prognosis than the others.