Proliferating cell nuclear antigen and heat shock protein 70 immuno-localization in invasive ductal breast cancer not otherwise specified

Abstract

A series of 80 female patients undergoing surgery for primary breast ductal infiltrating carcinoma not otherwise specified (NOS) was immunohistochemically studied in order to verify any relationships between Proliferating Cell Nuclear Antigen (PCNA) immunostaining, Heat Shock Protein 70 (HSP70) immunoreactivity, and several clinicopathological predictors. Positive PCNA scores (> 20% of strongly immunopositive malignant nuclei) were observed in neoplastic cells' nuclei in 13 tumors (16.25%) and were intimately associated with axillary nodal involvement (p = 0.0131), relatively high tumor grades (p = 0.0016), increased tumor size (p = 0.0312), and low or negative levels of estrogen receptors (p = 0.0323). HSP70 positive immunoexpression in malignant cells' cytoplasm (percentage of HSP70 immunoreactive cells > 10%) was detected in 33 samples (41.25%). It correlated significantly with presence of axillary lymph nodal metastases (p = 0.0033) and rather poor tumor differentiation (p = 0.0014), whereas an association of borderline statistical significance emerged between HSP70 immunoreactivity and high progesterone receptor status (p = 0.0637). PCNA positive immunostaining demonstrates the tumors' proliferative fraction and might be used as an indicator of increased malignant potential in breast cancer since it was associated with four adverse prognosticators. HSP70 immunodetection is a probable marker of the biological stress experienced by breast cancer cells, since it was related to relatively high tumor grades. Since both proteins may potentially predict disease outcome, their prognostic significance must be validated by direct relation to survival. A multivariate statistical analysis including the variables with which both proteins were associated will reveal any possible independent prognostic value of PCNA and HSP70 immunostaining in local, ductal invasive breast cancer NOS.

High interstitial fluid pressure promotes tumor cell proliferation and invasion in oral squamous cell carcinoma

“…Subsequently, we used qRT-PCR to confirm the pressure-dependent expression of over 20 genes identified in the microarray analysis. Heat shock protein (HSP)A4, also known as HSP70, has been shown to be significantly associated with low differentiation and poor prognosis in a number of malignant tumors (17)(18)(19). CCND1, also known as cyclin D1, is overexpressed in several human tumors; its expression is induced by growth factors and occurs at multiple levels, including increased transcription, translation and protein stability (20)(21)(22).…”

Elevated Serum Levels of Heat Shock Protein 70 Are Associated with Breast Cancer

“…Overexpression of HSP70 has been shown as a marker for advanced disease and lymph node metastasis in colorectal carcinoma (Lazaris et al 1997;Hwang et al 2003), BC and undifferentiated ovarian cancer (Athanassiadou et al 1998). In cervical cancer, it is correlated with tumor size and increased proliferation (Ralhan and Kaur 1995).…”

Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms

“…Hsp70 is abundantly expressed in malignant tumors of various origins (for review, see Jäättelä 1999), and its expression correlates with increased cell proliferation, poor differentiation, lymph node metastases, and poor therapeutic outcome in human breast cancer (Ciocca et al 1993;Lazaris et al 1997;Vargas-Roig et al 1997. Furthermore, numerous experimental cancer models have demonstrated the tumorigenic potential of Hsp70 in rodents (Jäättelä 1995;Seo et al 1996;Volloch and Sherman 1999;Gurbuxani et al 2001).…”