Beta-catenin expression patterns in matched pre- and post-neoadjuvant chemotherapy-resistant breast cancer.

BACKGROUND: ß-catenin is a critical component of the cadherin cell-to-cell adhesion pathway and a key participant in the Wnt signaling pathway. Activation of ß-catenin signaling in the Wnt pathway is a known contributor to tumor cancer progression and metastasis and may result in resistance to chemotherapeutic agents. The aim of this study is to evaluate the patterns of expression of ß-catenin in breast carcinoma cells before and after neoadjuvant chemotherapy. Discovery of the molecular mechanisms responsible for resistance to chemotherapy treatment could result in more effective therapy, and improve outcome and survival. DESIGN: Twenty-nine matched pre-treatment and post-neoadjuvant chemotherapy breast carcinomas were subjected to immunohistochemical study using anti-ß-catenin antibody. Normal staining was defined as crisp membrane staining in >90% tumor cells; aberrant expression was nuclear staining in >5% tumor cells. RESULTS: Of the 29 included cases, five cases of invasive lobular carcinoma lacked ß-catenin immunoreactivity pre- and post-treatment. Mildly reduced membranous staining was seen in two post-treatment samples. One case of triple-negative ductal carcinoma had reduced pre- and post-treatment staining. All other cases showed normal pre- and post-treatment ß-catenin expression. No aberrant staining was identified. CONCLUSION: In our study, there was no difference in the expression of ß-catenin in pre- and post-neoadjuvant chemotherapy specimens. These results do not suggest that ß-catenin plays a role in conferring neoadjuvant chemotherapy resistance.

Cytoplasmic Clusterin expression correlates with pancreatic neuroendocrine tumor size and pathological stage.

OBJECTIVES: Cytoplasmic clusterin (Clusterin), a ubiquitous multifunctional secretory sulfated glycoprotein, plays a role in apoptosis and is reportedly overexpressed in a variety of tumors. The role of Clusterin in pancreatic neuroendocrine tumors (PNETs) has not been investigated. In this study, Clusterin expression was evaluated in a subset of PNETs, and the results were correlated with the clinical-pathological features of the tumors. METHODS: Fifty-nine surgical cases were used to evaluate the immunohistochemical expression of Clusterin in PNETs. Using the avidin-biotin complex method, tissue sections from each case were stained with a rabbit anticlusterin antibody (Abcam, Cambridge, Mass). The immunohistochemical reactions were qualitatively and semiquantitatively evaluated by 2 pathologists. RESULTS: Strong Clusterin reactivity was identified in 36 (61%) of 59 PNETs. In 23 (39%) of 59 cases, the Clusterin score was 3 or less. Clusterin expression scores significantly associated with tumor size (P = 0.03) and with tumor stage (P = 0.02). The immunohistochemical score index did not correlate with tumor grade (P = 0.15). CONCLUSIONS: We report the expression of Clusterin in PNETs. The correlation of Clusterin with tumor size and stage suggests involvement of this molecule in pancreatic neuroendocrine tumor progression. Clusterin may represent a new target of therapy for PNETs.

Squamous cell carcinoma with rhabdoid phenotype of skin/soft tissue in a transplant patient: an exceptional case and review of the literature.

Squamous cell carcinoma with rhabdoid features (SCCRF) is a very rare and unusual cutaneous tumor. Here, we report an extraordinary case diagnosed by fine needle aspiration biopsy, in a 66-year-old man, status post multiple organ transplantation. The patient presented with a large ulcerating fungating mass in his forearm that had all the light microscopic and immunohistochemical features of a SCCRF. Previously six cases of SCCRF phenotype diagnosed by surgical pathology have been reported. This is the first case diagnosed cytologically. A review of the literature with emphasis on the differential diagnoses of such unusual rhabdoid-like tumors in fine-needle aspiration biopsy and the potential molecular mechanism for rhabdoid phenotype in transplant patients are discussed.

Primary colorectal adenocarcinoma metastatic to the breast: case report and review of nineteen cases.

Metastases to the breast from extramammary primaries are uncommon and account for 0.5-6% of all breast malignancies (Georgiannos et al., 2001, and Vizcaíno et al., 2001). Malignant melanoma, lymphoma, and lung and gastric carcinomas are the most frequently encountered nonmammary metastases to the breast in adults (Georgiannos et al., 2001, and Chaignaud et al., 1994). Primary colorectal adenocarcinoma (CRC) metastatic to the breast is extremely rare, with the medical literature having only 19 recorded cases. Typically CRC metastatic to the breast is indicative of widely disseminated disease and a poor prognosis. Here we present a case of poorly differentiated colon cancer metastatic to the breast and review the current literature on this rare event.

Squamous cell carcinoma and osteosarcoma arising from a dermoid cyst--a case report and review of literature.

A rare case of multiple malignant tumors (poorly differentiated squamous cell carcinoma and high grade osteosarcoma) arising in an ovarian dermoid cyst of a 55 year old female is reported. To the best of our knowledge, this is the first well documented example of such an unusual combination of tumors arising in a dermoid cyst. The osteosarcoma and squamous cell carcinoma appear to arise in the background of benign teratomatous environment of a dermoid cyst rather than from "pure" mixed mesodermal tumors of the ovary. The tumors did not appear to have well demarcated boundaries with a junction or close intermingling of both cell types, features less favorable for collision tumor or carcinosarcoma. Despite extensive surgery with negative surgical margins and combination chemotherapy, the patient had recurrence of the tumor within four months and she died secondary to septicemia to chemotherapy and bilateral pulmonary emboli shortly after.

Using image analysis as a tool for assessment of prognostic and predictive biomarkers for breast cancer: How reliable is it?

BACKGROUND: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) are important and well-established prognostic and predictive biomarkers for breast cancers and routinely tested on patient's tumor samples by immunohistochemical (IHC) study. The accuracy of these test results has substantial impact on patient management. A critical factor that contributes to the result is the interpretation (scoring) of IHC. This study investigates how computerized image analysis can play a role in a reliable scoring, and identifies potential pitfalls with common methods. MATERIALS AND METHODS: Whole slide images of 33 invasive ductal carcinoma (IDC) (10 ER and 23 HER2) were scored by pathologist under the light microscope and confirmed by another pathologist. The HER2 results were additionally confirmed by fluorescence in situ hybridization (FISH). The scoring criteria were adherent to the guidelines recommended by the American Society of Clinical Oncology/College of American Pathologists. Whole slide stains were then scored by commercially available image analysis algorithms from Definiens (Munich, Germany) and Aperio Technologies (Vista, CA, USA). Each algorithm was modified specifically for each marker and tissue. The results were compared with the semi-quantitative manual scoring, which was considered the gold standard in this study. RESULTS: For HER2 positive group, each algorithm scored 23/23 cases within the range established by the pathologist. For ER, both algorithms scored 10/10 cases within range. The performance of each algorithm varies somewhat from the percentage of staining as compared to the pathologist's reading. CONCLUSIONS: Commercially available computerized image analysis can be useful in the evaluation of ER and HER2 IHC results. In order to achieve accurate results either manual pathologist region selection is necessary, or an automated region selection tool must be employed. Specificity can also be gained when strict quality assurance by a pathologist is invested. Quality assurance of image analysis by pathologists is always warranted. Automated image analysis should only be used as adjunct to pathologist's evaluation.