Centrosome amplification: a quantifiable cancer cell trait with prognostic value in solid malignancies.

Numerical and/or structural centrosome amplification (CA) is a hallmark of cancers that is often associated with the aberrant tumor karyotypes and poor clinical outcomes. Mechanistically, CA compromises mitotic fidelity and leads to chromosome instability (CIN), which underlies tumor initiation and progression. Recent technological advances in microscopy and image analysis platforms have enabled better-than-ever detection and quantification of centrosomal aberrancies in cancer. Numerous studies have thenceforth correlated the presence and the degree of CA with indicators of poor prognosis such as higher tumor grade and ability to recur and metastasize. We have pioneered a novel semi-automated pipeline that integrates immunofluorescence confocal microscopy with digital image analysis to yield a quantitative centrosome amplification score (CAS), which is a summation of the severity and frequency of structural and numerical centrosome aberrations in tumor samples. Recent studies in breast cancer show that CA increases across the disease progression continuum, while normal breast tissue exhibited the lowest CA, followed by cancer-adjacent apparently normal, ductal carcinoma in situ and invasive tumors, which showed the highest CA. This finding strengthens the notion that CA could be evolutionarily favored and can promote tumor progression and metastasis. In this review, we discuss the prevalence, extent, and severity of CA in various solid cancer types, the utility of quantifying amplified centrosomes as an independent prognostic marker. We also highlight the clinical feasibility of a CA-based risk score for predicting recurrence, metastasis, and overall prognosis in patients with solid cancers.

Metaplastic variant of invasive micropapillary breast carcinoma: a unique triple negative phenotype.

Invasive micropapillary carcinomas (IMC) and metaplastic breast carcinoma (MBC) have different clinicopathologic features. This study reports an unusual case of multifocal grade III IMC associated with MBC component in a 35-year-old woman. MBC was vimentin positive, pancytokeratin negative, and showed focal p63 positivity. Immunostains for estrogen and progesterone receptor, and fluorescence in situ hybridization for Her2/neu amplification were negative. All the left axillary lymph nodes dissected were positive for metastatic carcinoma with ductal and IMC patterns, but without metaplastic component. Postmastectomy computed tomography and magnetic resonance imaging scans showed metastases to lungs, liver, brain, and vertebrae. The biologic behavior of tumor was in accordance with histology, so that the nodal and distant metastases were testament to the underlying inherently aggressive IMC, whereas large tumor size and triple negativity reflected the features of MBC. To the best of the authors' knowledge, this is the first report of a metaplastic variant of invasive micropapillary breast carcinoma with triple negative phenotype.