Mireia Castillo

Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands.

Mucins are glycoproteins normally synthesized by a variety of secretory epithelial cells. The aim of this study was to investigate the expression of mucins (MUC1, MUC2, MUC4, MUC5AC, MUCB, MUC6, MUC7) in mucoepidermoid carcinomas, the most frequent malignant tumor of salivary glands. Forty mucoepidermoid carcinomas and twenty-two normal salivary glands were studied for these mucins by immunohistochemistry from formalin-fixed and paraffin-embedded material. Normal salivary glands frequently expressed MUC1 and MUC4, mainly in ductal cells; MUC5B and MUC7 stained mucous and serous acini respectively of submandibular and minor salivary glands; and MUC5AC and MUC2 were poorly detected in excretory ducts. All mucoepidermoid carcinomas expressed MUC1, and 38/40 tumors expressed MUC4. Both membrane-bound mucins stained membranes and cytoplasm of all cell types (epidermoid, intermediate, mucous, clear and columnar). MUC5AC and MUC5B stained glandular differentiated cells in most tumors (29/40 and 33/40 cases, respectively). MUC6 was positive in 13/40 tumors, and both MUC2 and MUC7 in only 2/40 tumors. The high expression of MUC1 was related to high histologic grades, high recurrence and metastasis rates and a shorter disease-free interval (P < 0.05). Conversely, MUC4 high expression was mainly related to low-grade tumors, lower recurrence rates and a longer disease-free interval (P < 0.05). In conclusion, mucoepidermoid carcinomas of salivary glands usually express MUC1, MUC4, MUC5AC and MUC5B; less frequently MUC6; and rarely MUC2 and MUC7. This mucin expression pattern can be useful for diagnostic purposes. Therefore, MUC1 expression is related to tumor progression and worse prognosis, whereas MUC4 expression is related to a better prognosis.

KIT expression in chromophobe renal cell carcinoma: Comparative immunohistochemical analysis of KIT expression in different renal cell neoplasms

The overexpression of c-Kit in chromophobe renal cell carcinoma (ChRCC) has been described by comparative gene expression analyses and has been proposed as a possible specific hallmark of this neoplasm. The aim of our study was to establish its immunohistochemical expression in a large series of ChRCC and to compare it with other renal neoplasms. In our study, immunohistochemical characterization of KIT was performed in 87 renal neoplasms including 25 cases of ChRCC, 13 cases of renal oncocytoma, and 39 renal cell carcinomas (21 cases of conventional RCC [CRCC], 8 cases of CRCC with granular cell differentiation, and 10 cases of papillary RCC [PRCC]). Eighty-eight percent ChRCC and 71% oncocytomas showed immunohistochemical expression of KIT, while the other types of RCC studied were all negative. The meaning of immunohistochemical expression of KIT in ChRCC and oncocytomas is still unknown, but its immunohistochemical staining appears to be useful in distinguishing ChRCC from PRCC, CRCC, and its granular cell variant. Moreover, our findings support current models that consider that there is a histopathogenic relationship between oncocytoma and ChRCC. Finally, it should be determined whether KIT plays a role in the tumorigenesis of ChRCC and oncocytoma and whether targeted therapy with STI-571, an inhibitor of KIT, could be effective in exceptional cases of ChRCC with metastatic extension or recurrence.

Immunohistochemical expression of CK20, p53, and Ki-67 as objective markers of urothelial dysplasia

Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Distinguishing CIS and dysplasia from reactive atypia is often difficult on the basis of histological features alone. Cytokeratin 20 (CK20), p53, and Ki-67 are related either to neoplastic change or prognosis in urothelial proliferations. The objective of the present study was to establish the immunohistochemical pattern of these three antibodies in urothelial dysplasia and CIS. Three groups of patients were evaluated: 40 nonneoplastic urothelial samples, 50 cases with histologically incontrovertible CIS, and 30 samples with nonconclusive atypical changes (atypia of unknown significance). Monoclonal antibodies (MoAb) against CK20, p53, and Ki-67 (MIB-1) were used on paraffin-embedded samples. Nonneoplastic urothelium showed no reactivity to CK20 except for umbrella cells; p53 and Ki-67 were negative or weakly positive in <10% of basal cells. In the CIS group, 42% showed positivity for all three MoAb; 44%, for two; and 14%, only for one. CK20 was positive through the full thickness of the urothelium in 72% of cases, p53 was positive in 80% of cases, and Ki-67, in 94% of cases. In the third group, the suspected dysplastic cells showed strong positivity in scattered cells through the epithelium in 75% of cases. Aberrant CK20 expression in urothelial cells plus overexpression of p53 and Ki-67 are indicators of dysplastic change in urothelial mucosa. Thus, immunohistochemistry is a useful tool to confirm the diagnosis of CIS and could be helpful to distinguish dysplastic changes from reactive atypia.

Adenosquamous carcinoma of the head and neck: criteria for diagnosis in a study of 12 cases

Aims:  Adenosquamous carcinoma (ASC) of the head and neck is an unusual neoplasm in which a general consensus with regard to diagnostic criteria has not yet been reached. In this study we report the clinicopathological results of 12 ASCs, with special attention to their histological and immunohistochemical characteristics in order to define this neoplasm more precisely.

Routine use of immunophenotype by flow cytometry in tissues with suspected hematological malignancies

Immunophenotype is an essential parameter in the diagnosis of hematological malignancies. Flow cytometry (FCM) is used in the analysis of bone marrow or peripheral blood samples but is less frequently used in the evaluation of tissue biopsies with suspected hematological malignancies. The aim of this study was to analyze the role of FCM in the diagnosis of biopsies from patients with a suspected hematological disorder.

Paraffin-Embedded Cell Line Microarray (PECLIMA): Development and Validation of a High-Throughput Method for Antigen Profiling of Cell Lines

The introduction of high-throughput techniques is increasingly providing abundant information on molecular alterations requiring validation at the posttranscriptional level. Protein expression is now efficiently evaluated in large series of tumors included in tissue microarrays. We propose, describe and validate a technique to elaborate paraffin-embedded cell line microarrays (PECLIMA) from fixed cell cultures, which can be processed like standard surgical pathology biopsies prior to immunophenotyping. Our results show a reliable protein immunoexpression profiling in six widely used cell lines under different fixation conditions. This technique permits the simultaneous analysis of multiple antigens in multiple cell lines under different experimental conditions. Additional features of these arrays are long-term storage, their suitability for a variety of techniques including immunocytochemistry and in situ hybridization and their low cost.

Carcinosarcoma of the prostate: two cases with distinctive morphologic and immunohistochemical findings

Carcinosarcomas (CS) of the prostate are very uncommon neoplasms defined by the admixture of malignant epithelial and mesenchymal components. We describe here two new examples of CS in two patients aged 66 and 77 years, the first without previous history of prostate adenocarcinoma and the second with a 5-year history of acinar type prostate adenocarcinoma. The diagnosis of CS was made on the cystoprostatectomy specimen in the first case and transurethral resection in the second case. Both biphasic tumours exhibited papillary areas of ductal differentiation and conventional adenocarcinoma in the epithelial component, as well as malignant fibrous histiocytoma and angiosarcomatous areas in the first case and solid, poorly differentiated epithelial areas with neuroendocrine features in the second case. Immunohistochemistry revealed over-expression of c-erb B2 in the papillary epithelial component of both cases, whereas the solid undifferentiated epithelial areas in the second patient expressed c-kit, CD10 and synaptophysin, thus conforming a very undifferentiated cell population. The angiosarcomatous component of the first case expressed CD31 and CD10. The clinical course of the cases was divergent; the first patient is free of disease after radical surgery and adjuvant therapy and the other died 5 months after the diagnosis of CS, having already developed liver metastases.