Mary Iacocca

The somatic genomic landscape of glioblastoma.

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype

Focal adhesion kinase (FAK) is a protein tyrosine kinase expressed in invasive breast cancer that regulates antiapoptotic signaling. We have examined FAK expression by immunohistochemistry using anti-FAK 4.47 in breast tumor samples from a large population-based, case–control study of women participating in the University of North Carolina Breast Specialized Programs of Research Excellence (SPORE), Carolina Breast Cancer Study. In this population, 629 formalin-fixed, paraffin-embedded tissue sections were stained for FAK and scored as high (3+ or 4+ intensity and ≥90% positive cells) or otherwise. High FAK expression was associated with poor prognostic indicators including high mitotic index (>10 mitoses per 10 consecutive high-power fields), nuclear grade 3, architectural grade 3, estrogen and progesterone receptor negative, and HER-2/neu overexpressed using CB11 antibody. The association of high FAK expression with HER-2/neu overexpression lends further support that HER-2/neu and FAK collaborate to promote tumorigenesis. The presence of strong FAK expression in many high grade, estrogen- and progesterone-negative breast carcinomas indicates that FAK may be an attractive target for therapeutic intervention.

HER2 codon 655 polymorphism and risk of breast cancer in African Americans and whites.

AbstractBackground. Several recent epidemiologic studies examined the association between breast cancer risk and an inherited, single-nucleotide polymorphism in the HER2 gene, codon 655 G to A, which leads to an amino acid substitution of Ile to Val. Results of previous studies have been mixed, with most studies showing no association but some suggesting an association in younger women or women with a family history of breast cancer. Methods. We conducted an association study of HER2 codon 655 genotype and breast cancer within the Carolina Breast Cancer study, a population-based, case-control study of in situ and invasive breast cancer in African American and white women in North Carolina. A total of 2015 cases and 1808 controls were genotyped. Results. We observed no overall association between HER2 genotype and breast cancer. However, a modest positive association (OR = 2.3, 95% CI 1.0–5.3) was observed for Val/Val + Ile/Val versus Ile/Ile genotypes in women age 45 or younger with a family history of breast cancer. Val/Val homozygotes were more common among cases with in situ versus invasive disease (P = 0.002). Breast tumors from women with Val/Val genotype were more likely to exhibit HER2 overexpression, but the results were not statistically significant (P = 0.17). Conclusions. The HER2 codon 655 polymorphism may be one of many low-penetrant genes that make a minor contribution to breast cancer, particularly in subgroups of women. Additional large studies, as well as data pooling, will be needed to estimate the contribution of such genes to breast cancer risk.

Cytokeratin immunohistochemical validation of the sentinel node hypothesis in patients with breast cancer

No standard method for handling and histopathologic examination of the sentinel node (SN) exists. We hypothesized that a focused examination of all nodes with serial sectioning and cytokeratin immunohistochemical staining would confirm the SN as the node most likely to harbor metastasis. Intraoperative lymphatic mapping and sentinel lymphadenectomy using blue dye and (99m)technetium-labeled sulfur colloid were performed. All nodes were stained with H&E. All tumor-free nodes underwent additional sectioning and staining with H&E and an immunohistochemical stain. Routine H&E examination detected SN metastases in 27.6% of cases. Occult SN metastases were identified in 12.7% of cases. None of the 724 non-SNs examined contained occult metastases. The SN false-negative rate was zero. This study confirms histopathologically that the SN has biologic significance as the axillary node most likely to harbor metastatic tumor Standardization of the handling, sectioning, and staining of the SN is necessary as lymphatic mapping and sentinel lymphadenectomy become integrated into the care of patients with breast cancer

Comparing capsule exposure using extracapsular dissection with partial superficial parotidectomy for pleomorphic adenoma

UNLABELLED The aim of this study was to compare capsule exposure using extracapsular dissection (ECD) with partial superficial parotidectomy (PSP) for pleomorphic adenoma. PURPOSE Long-term favorable results for recurrence and facial nerve function have been reported for ECD and PSP for parotid pleomorphic adenoma. Extracapsular dissection is distinguished from PSP in that the facial nerve is dissected in PSP but not in ECD. This article attempts to answer the following hypothesis: the margin of normal parotid tissue surrounding a parotid pleomorphic adenoma is less for ECD compared with PSP. MATERIAL AND METHODS This is a retrospective individual case-control study. Twelve consecutive parotidectomy procedures with a final pathology report of pleomorphic adenoma were retrospectively measured for margin (the percent of capsule exposure around the tumor). In 8 highly selected patients, ECD was performed. Four parotid surgical procedures not meeting strict criteria underwent PSP and served as controls. RESULTS The eight patients with ECD had a mean of 80% (71%-99%) of the capsule exposed. The 4 PSP procedures had 21% (4%-50%) of the capsule exposed (P < .05). CONCLUSIONS Extracapsular dissection results in higher capsule exposure.

Bilateral Infiltrating Lobular Carcinoma of the Breast with Osteoclast-Like Giant Cells

Abstract: A case of bilateral infiltrating lobular carcinoma of the breast containing osteoclast‐like giant cells is presented. Notable pathologic features include prominent tumor‐associated angiogenesis and the presence of osteoclast‐like giant cells in axillary lymph node metastases. Immunohistologic and ultrastructural examination support a nonepithelial, histiocytic origin for the giant cells, and results are similar to previous reports of osteoclast‐like giant cells associated with breast carcinoma. This is the first report of bilateral pure infiltrating lobular carcinoma of the breast with osteoclast‐like giant cells and the first case of pure lobular carcinoma with osteoclast‐like giant cells present in lymph node metastases.

Ruptured extratesticular epidermal inclusion cyst mimicking polyorchidism with torsion on sonography

The sonographic appearance of epidermal inclusion cysts varies in accordance with the contents of the cyst, ranging from an anechoic lesion to a hyperechoic solid appearing mass. Supernumerary testes are an uncommon congenital abnormality, in which more than two testes are present. We present a rare case of a ruptured scrotal extratesticular epidermal inclusion cyst, which had the sonographic appearance of a supernumerary testicle with torsion.