In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23%) of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001); in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively). No relationship was evident with tumour size (T) and regional lymph node (N) status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004). Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.

Breast-like vulvar lesion with concurrent breast cancer: a case report and critical literature review.

In the current report, we describe an intriguing case of a breast-like cancer lesion located in the vulvar region in a woman lacking a remarkable past medical or family history of breast cancer but with concurrent breast cancer. Consequently, a differential diagnosis between a primary synchronous breast and vulvar cancer or a metastatic breast carcinoma to the vulva is a key point in terms of the clinical approach. In a review of the literature, 39 cases of breast-like cancer lesion have been described: 23 cases of primary infiltrating carcinoma of the vulva and 16 cases of vulvar metastases of breast carcinoma. To the best of our knowledge, this is the first report of a clinically synchronous vulvar metastasis from an invasive ductal carcinoma. The main diagnostic criteria for differential diagnosis between primary or metastatic breast-like vulvar carcinoma are also discussed.

Caveolin-1 expression in human breast lobular cancer progression.

Caveolin-1 is the principal structural protein of caveolae, and caveolin-1 gene plays a role as a tumour suppressor gene in human mammary cancer-derived cells. However, limited data are available concerning caveolin-1 expression in human breast cancer tissue. We evaluated caveolin-1 expression in normal lobular epithelial cells and in the whole human lobular neoplasia spectrum disease, with the aim to examine differences of caveolin-1 expression in human lobular neoplasia progression. We selected 147 cases of pure lobular lesions, ie lobular intraepithelial neoplasia and invasive lobular carcinoma, from 112 patients. Presence of caveolin-1 was evaluated by immunohistochemistry. Among 81 lobular intraepithelial neoplasia lesions studied, 43% were associated with invasive lobular carcinoma, with positive correlation between lobular intraepithelial neoplasia grade and presence of invasive component (P=0.01). In total, 64% of lobular lesions were positive for caveolin-1 (81% lobular intraepithelial neoplasia and 42% invasive lobular carcinoma), and a significant difference in terms of caveolin-1 expression was present between lobular intraepithelial neoplasia and invasive lobular carcinoma (P=0.0001). Variations in caveolin-1 expression were evident among the different lobular intraepithelial neoplasia grades (91% grade 1, 68% grade 2, 35% grade 3); the difference was significant comparing lobular intraepithelial neoplasia grade 3 vs 1 (P=0.0001) and grade 3 vs 2 (P=0.007) but not grade 1 vs 2. Furthermore, significant differences were found between lobular intraepithelial neoplasia grades 1 and 2 vs invasive lobular carcinoma (P=0.0001), but not between lobular intraepithelial neoplasia grade 3 and invasive lobular carcinoma (P=0.196). In conclusion, variations of caveolin-1 expression may have an important role in the progression of human breast lobular cancer; in addition, they confirm the powerful clinical impact of the lobular intraepithelial neoplasia classification for lobular intraepithelial neoplasia, supporting the direct origin of invasive lobular carcinoma from clonal expansion of the lobular intraepithelial neoplasia lesions cells.

COX-2 localization within plasma membrane caveolae-like structures in human lobular intraepithelial neoplasia of the breast.

Cyclooxygenase-2 (COX-2) is highly expressed in human intraepithelial neoplasia of the breast and takes part in the molecular pathway implicated in progression of breast cancer. Recently, we demonstrated that COX-2 protein is mainly located in plasma membrane of lobular intraepithelial neoplasia (LIN) cells suggesting a localization in caveolae-like structures. The aim of the present study is to establish subcellular locations of COX-2 and its colocalization with caveolin-1 (CAV-1) to caveolae structures in LIN. To establish a relationship between COX-2 and CAV-1, 39 LINs were studied by immunohistochemistry and confocal microscopy analysis. COX-2 and CAV-1 expression was observed respectively in 79.5 and in 94.9% of LIN studied. A positive correlation was found between membrane COX-2 staining pattern and CAV-1 expression, while no correlation was found between cytoplasm COX-2 staining pattern and CAV-1. Confocal analysis showed that COX-2 localized to plasma membrane was strictly associated to CAV-1 suggesting that an amount of COX-2 protein is placed in caveolae-like structures. Our results show that COX-2 is localized within caveolae compartment and colocalized with CAV-1 protein in LIN lesions. Because caveolae are rich in signaling molecules, this COX-2 compartment may play an important role in diverse breast cancer carcinogenesis processes.

Immunohistochemistry and differential diagnosis of a solitary flat laryngeal xanthoma: a case report.

A 35-year-old woman presented with dyspnea, recurrent laryngitis and gastroesophageal reflux disease. Laryngoscopic examination revealed a yellow lesion on the anterior site of the left true vocal cord. No abnormal lesions were found in other portions of the larynx. The lesion was biopsied and a histological examination showed numerous foamy cells diffusely presented in the stroma of the specimen. Overlying squamous epithelium did not show cellular atypia. On the basis of histological appearance, the possible differential diagnosis included xanthomatous lesion, granular cell tumor or epithelial neoplasia. CD68, S-100 protein and cytokeratin immunoreactivities were investigated. Immuno-histochemically, foamy cells were positive for CD68, indicating a histiocytic origin.

Reelin expression in human prostate cancer: a marker of tumor aggressiveness based on correlation with grade.

Reelin is a glycoprotein that plays a critical role in the regulation of neuronal migration during brain development and, since reelin has a role in the control of cell migration, it might represents an important factor in cancer pathology. In this study, 66 surgical specimens of prostate cancer were analyzed for reelin expression by immunohistochemical method. The reelin expression was correlated with Gleason score and individual Gleason patterns. Reelin expression was found in 39% prostate cancers. Stromal tissues, normal epithelial cells and prostate intraepithelial neoplasia (PIN) of any grade around and distant from cancer were always negative for reelin. Reelin was found in malignant prostatic epithelial glands of 50% cases Gleason score 10, 52% Gleason score 9, 56% Gleason score 8, 18% Gleason score 7, while no sample of prostate cancers with Gleason score 6 showed reelin expression (P=0,005). As reelin staining is frequently found in high Gleason score prostate cancers, we explored whether reelin expression is influenced by single Gleason patterns. While Gleason 3 pattern did not show reelin immunoreactivity, reelin expression was found in 35% Gleason 4 patterns and 45% Gleason 5 patterns (P<0.001). Our results demonstrated for the first time that reelin is expressed in prostate cancer and not in benign prostate tissue and its expression occurs in higher Gleason score and correlates significantly with increasing of single Gleason patterns. This suggests reelin may behave as a specific histological marker and may represent a useful biomarker to predict aggressive phenotypic behavior of prostatic cancer cells.

COX-2 expression of ampullary carcinoma: correlation with different histotypes and clinicopathological parameters.

Epidemiological studies suggest that regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced incidence of gastrointestinal cancer. Several lines of evidence indicate that the antineoplastic effect of NSAIDs is attributable to COX-2 inhibition. The aim of our study was to assess COX-2 expression in a series of primary untreated ampullary carcinomas and its possible correlation with clinicopathological parameters. In the present study, 45 surgical specimens of invasive ampullary carcinomas were histologically classified into pancreaticobiliary, intestinal, and unusual types. COX-2 expression by immunohistochemical method was analyzed. High COX-2 expression was detected in 35 (77.8%) ampullary carcinomas. Among these, 20/21 (95.2%) were classified as intestinal, 9/18 (50%) pancreaticobiliary, and 6/6 (100%) unusual type. A significant statistical difference in terms of COX-2 expression was found between pancreaticobiliary vs intestinal type (P=0.002). Furthermore, a negative significant statistical correlation was found between T factor and COX-2 expression (P=0.047). The different COX-2 expression among histopathological types supports the concept of histogenetical difference of ampullary carcinomas. Furthermore, the high rate of COX-2 expression in the intestinal subtype of ampullary carcinoma may represent the rational for a histotype-tailored therapy targeting COX-2.