scholarly journals Do the Survivin (BIRC5) Splice Variants Modulate or Add to the Prognostic Value of Total Survivin in Breast Cancer?

2006 ◽  
Vol 52 (9) ◽  
pp. 1693-1700 ◽  
Author(s):  
Paul N Span ◽  
Vivianne CG Tjan-Heijnen ◽  
Joop JTM Heuvel ◽  
Jacques B de Kok ◽  
John A Foekens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Value ◽  
Hormone Receptors ◽  
Splice Variants ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Mrna Levels ◽  
Relapse Free Survival ◽  
Clinicopathologic Characteristics ◽  
Free Survival

Abstract Background: A total of 4 additional splice variants (survivin-ΔEx3, survivin 2α, survivin-2B, and survivin-3B) have been described for survivin [baculoviral IAP repeat-containing protein (BIRC-5), approved gene symbol BIRC5], which has been implicated in both inhibition of apoptosis and regulation in mitosis in many tumor types. In this study, we assessed whether the survivin splice variants modulate or add to the prognostic value of total survivin in breast cancer. Methods: With quantitative reverse transcription-PCR, we measured mRNA concentrations of survivin and all variants in tumor tissue from 275 patients with breast cancer and associated these with clinicopathologic characteristics and relapse-free survival. Results: Total survivin, survivin-ΔEx3, and survivin 2α mRNA levels were associated with young age and ductal histology. Total survivin and survivin-ΔEx3 were highest in samples with advanced histological grade, whereas patients with 4–9 involved lymph nodes expressed less survivin-2B mRNA than those with 1–3 involved nodes. All variants were higher in tumors negative for steroid hormone receptors. Total survivin, survivin 2α, and survivin-3B were associated with poor relapse-free survival in univariate analyses. Survivin 2α and survivin-3B added to the prognostic value of total survivin in multivariate analyses. In addition, the prognostic value of total survivin was evident only in the presence of higher expression levels of these 2 variants. Conclusions: All variants of survivin exhibited particular associations with clinicopathologic characteristics (age, histology, grade, and steroid hormone receptor status) of breast cancer patients. Survival analyses suggest a modulating role of survivin 2α and survivin-3B on the biological function of total survivin.

Pepsinogen C is a new prognostic marker in primary breast cancer.

1995 ◽  
Vol 13 (1) ◽  
pp. 54-61 ◽  
Author(s):  
F Vizoso ◽  
L M Sánchez ◽  
I Díez-Itza ◽  
A M Merino ◽  
C López-Otín
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Value ◽  
Survival Duration ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Node Negative ◽  
Pepsinogen C ◽  
Node Positive

PURPOSE Here we evaluate in breast cancer patients the prognostic value of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant percentage of breast carcinomas. PATIENTS AND METHODS Pepsinogen C expression was examined by immunoperoxidase staining in a series of 243 breast cancer tissue sections, and results obtained were quantified using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. Evaluation of the prognostic value of pepsinogen C was performed retrospectively in corresponding patients by multivariate analysis that took into account conventional prognostic factors. The mean follow-up period was 48.5 months. RESULTS A total of 113 carcinomas (46.5%) stained positively for this proteinase, but there were clear differences among them with regard to the intensity and percentage of stained cells. Pepsinogen C values were significantly higher in well differentiated (grade I, 89.1) and moderately differentiated (grade II, 88.5) tumors than in poorly differentiated (grade III, 27.7) tumors (P < .001). Similarly, significant differences in pepsinogen C content were found between estrogen receptor (ER)-positive tumors and ER-negative tumors (85.9 v 41.2, respectively; P < .05). Moreover, results indicated that low pepsinogen C content predicted shorter relapse-free survival duration and overall survival duration (P < .0001). Separate Cox multivariate analysis for relapse-free survival and overall survival in subgroups of patients as defined by node status showed that pepsinogen C expression was the strongest factor to predict both relapse-free survival and overall survival in node-positive patients (P < .0001 for both) and node-negative patients (P < .005 and P < .01, respectively). CONCLUSION Pepsinogen C is a new prognostic factor for early recurrence and death in both node-positive and node-negative breast cancer. In addition, and in contrast to most studies that concern the prognostic significance of proteolytic enzymes in cancer, pepsinogen C production by breast cancer cells is associated with lesions of favorable evolution.

scholarly journals A critical review why assessment of steroid hormone receptors in breast cancer should be quantitative

2013 ◽  
Vol 24 (1) ◽  
pp. 47-53 ◽  
Author(s):  
O. Brouckaert ◽  
R. Paridaens ◽  
G. Floris ◽  
E. Rakha ◽  
K. Osborne ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Critical Review ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors

Meeting Highlights: Updated International Expert Consensus on the Primary Therapy of Early Breast Cancer

2003 ◽  
Vol 21 (17) ◽  
pp. 3357-3365 ◽  
Author(s):  
Aron Goldhirsch ◽  
William C. Wood ◽  
Richard D. Gelber ◽  
Alan S. Coates ◽  
Beat Thürlimann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Ductal Carcinoma ◽  
Steroid Hormone ◽  
Endocrine Resistance ◽  
Steroid Hormone Receptors ◽  
Average Risk ◽  
Primary Therapy ◽  
High Quality ◽  
The Impact

This account of the highlights of the eighth St Gallen (Switzerland) meeting in 2003 emphasizes new information that has emerged during the 2 years since the seventh meeting in 2001. This article should be read in conjunction with the report of that earlier meeting. Recommendations for patient care are so critically dependent on assessment of endocrine responsiveness that the importance of high-quality steroid hormone receptor determination and standardized quantitative reporting cannot be overemphasized. The International Consensus Panel modified the risk categories so that only endocrine receptor–absent status was sufficient to reclassify an otherwise low-risk, node-negative disease into the category of average risk. Absence of steroid hormone receptors also was recognized as indicating endocrine nonresponsiveness. Some important areas highlighted at the recent meeting include: (1) recognition of the separate nature of endocrine-nonresponsive breast cancer—both invasive cancers and ductal carcinoma-in-situ; (2) improved understanding of the mechanisms of acquired endocrine resistance, which offer exciting prospects for extending the impact of successful sequential endocrine therapies; (3) presentation of high-quality evidence indicating that chemotherapy and tamoxifen should be used sequentially rather than concurrently; (4) availability of a potential alternative to tamoxifen for treatment of postmenopausal women with endocrine-responsive disease; and (5) the promise of newly defined prognostic and predictive markers.

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