Expression of C4.4A, a Structural uPAR Homolog, Reflects Squamous Epithelial Differentiation in the Adult Mouse and during Embryogenesis

The glycosylphosphatidylinositol (GPI)–anchored C4.4A was originally identified as a metastasis-associated protein by differential screening of rat pancreatic carcinoma cell lines. C4.4A is accordingly expressed in various human carcinoma lesions. Although C4.4A is a structural homolog of the urokinase receptor (uPAR), which is implicated in cancer invasion and metastasis, no function has so far been assigned to C4.4A. To assist future studies on its function in both physiological and pathophysiological conditions, the present study provide a global survey on C4.4A expression in the normal mouse by a comprehensive immunohistochemical mapping. This task was accomplished by staining paraffin-embedded tissues with a specific rabbit polyclonal anti-C4.4A antibody. In the adult mouse, C4.4A was predominantly expressed in the suprabasal layers of the squamous epithelia of the oral cavity, esophagus, non-glandular portion of the rodent stomach, anus, vagina, cornea, and skin. This epithelial confinement was particularly evident from the abrupt termination of C4.4A expression at the squamo-columnar transition zones found at the ano-rectal and utero-vaginal junctions, for example. During mouse embryogenesis, C4.4A expression first appears in the developing squamous epithelium at embryonic day 13.5. This anatomical location of C4.4A is thus concordant with a possible functional role in early differentiation of stratified squamous epithelia.     

The Urokinase Receptor Homolog Haldisin Is a Novel Differentiation Marker of Stratum Granulosum in Squamous Epithelia

Several members of the Ly-6/uPAR (LU)-protein domain family are differentially expressed in human squamous epithelia. In some cases, they even play important roles in maintaining skin homeostasis, as exemplified by the secreted single domain member, SLURP-1, the deficiency of which is associated with the development of palmoplantar hyperkeratosis in the congenital skin disorder Mal de Meleda. In the present study, we have characterized a new member of the LU-protein domain family, which we find to be predominantly expressed in the stratum granulosum of human skin, thus resembling the expression of SLURP-1. In accordance with its expression pattern, we denote this protein product, which is encoded by the LYPD5 gene, as Haldisin (human antigen with LU-domains expressed in skin). Two of the five human glycolipid-anchored membrane proteins with multiple LU-domains characterized so far are predominantly confined to squamous epithelia (i.e., C4.4A), to stratum spinosum, and Haldisin to stratum granulosum under normal homeostatic conditions. Whether Haldisin is a prognostic biomarker for certain epithelial malignancies, like C4.4A and SLURP-1, remains to be explored.     

Changed expression of 9-O-acetyl GD3 (CDw60) in benign and atypical proliferative lesions and carcinomas of the human breast

 Expression of gangliosides is affected in various ways by malignant cell transformation. In the present study, we investigated the expression of CDw60, a constituent of O-acetylated disialogangliosides, in benign and atypical proliferative breast diseases, and preinvasive and invasive carcinomas by immunohistochemistry and thin-layer chromatography (TLC). In normal ducts, antibodies to CDw60 (mAb M-T21) reacted to membranes of the Golgi apparatus in the juxtaluminal cell compartment. A similar polarized distribution of Golgi cisterns in epithelial cells was observed in several benign lesions, i.e., fibroadenomas, intraductal papillomas, and gynecomastia. In contrast, blunt duct adenosis and duct hyperplasia exhibited an abnormal cytosolic and cell surface staining, whereas atypical duct hyperplasia showed randomly dispersed immunoreactive Golgi cisterns, indicating loss of epithelial polarity. In mammary carcinomas and in two breast carcinoma cell lines (MCF-7 and EFM-19) the neoplastic cells contained CDw60-immunolabelled Golgi complexes, which were distributed in a disorderly fashion throughout the cytoplasm, thus reflecting a loss of epithelial polarity. Additionally, only well differentiated ductal carcinomas in situ or invasive ductal carcinomas disclosed a strong cell surface labelling, which was absent in lower differentiated carcinomas of the same types. In all carcinomas, the intensity of CDw60 immunostaining decreased with progressing loss of differentiation (grade of dedifferentiation), as demonstrated by staining intensity in paraffin sections and by evaluation of the relative amounts of extracted 9-O-acetyl GD3 by TLC. Our results indicate that abnormal CDw60 expression is already detectable in benign proliferative breast lesions with different risk rates to develop into malignant lesions. Downregulation of CDw60 expression in poorly differentiated invasive carcinomas may be the consequence of loss of cell functions usually associated with poor prognosis. Received: 19 February 1998     

Increased incidence of squamous cell carcinomas in Mastomys natalensis papillomavirus E6 transgenic mice during two-stage skin carcinogenesis

Papillomaviruses cause certain forms of human cancers, most notably carcinomas of the uterine cervix. In contrast to the well-established involvement of papillomavirus infection in the etiology of cervical carcinomas and in carcinomas of a rare hereditary condition, epidermodysplasia verruciformis, a causative role for cutaneous human papillomavirus types in the development of nonmelanoma skin cancer has not been proven. In order to better understand the functions of individual genes of cutaneous papillomavirus types, we generated transgenic mice carrying oncogene E6 of the Mastomys natalensis papillomavirus (MnPV), which causes keratoacanthomas of the skin in its natural host. In the present study, we demonstrate that under conditions of experimental two-stage skin carcinogenesis, fast-paced squamous cell carcinomas develop in nearly 100% of MnPV E6 transgenic mice in comparison to 10% in their nontransgenic littermates (log rank test; P < 0.0001). Therefore, we conclude that the MnPV E6 transgene favors the malignant progression of chemically induced tumors. Whereas an activating H-ras mutation is a consistent feature in benign and malignant tumors in wild-type mice, the majority of papillomas and keratoacanthomas and all squamous cell carcinomas obtained in MnPV E6 transgenic mice contain nonmutated ras alleles. These results indicate that the development of squamous cell carcinomas in MnPV E6 transgenic mice does not depend on an activated H-ras oncogene.     

Expression of cytokeratin 19 and protein p63 in fine needle aspiration biopsy of papillary thyroid carcinoma

OBJECTIVE: To analyze the immunocytochemical distribution of CK19 and p63 on archival cytologic smears of 27 papillary thyroid carcinomas (PTCs), 22 benign thyroid lesions and 5 malignant non-PTC lesions. STUDY DESIGN: Archival cytologic smears of 27 papillary carcinomas, 22 benign thyroid lesions and 5 malignant nonpapillary carcinomas were processed for immunocytochemical detection of CK19 and p63, and results were compared. RESULTS: CK19 showed strong cytoplasmic staining in 22/27 fine needle aspiration biopsies (FNABs) of PTCs, in 5 benign lesions and in 4 malignant lesions of the control group. p63 Positivity was present in FNABs of 20/27 PTC and in 1 FNAB of nodular hyperplasia. Eighteen FNABs of PTC (66.6%) showed both strong CK19 staining and p63-positive cells, whereas none of the control cases showed coexpression of CK19 and p63. CONCLUSION: Coexistence of strong CK19 positivity and p63-positive cells can enhance the cytologic diagnosis of PTC.     

Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions

The matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes, which are responsible for the breakdown of the extracellular matrix components in pathological and physiological conditions. They are involved in basement membrane disruption, stroma and blood vessel penetration, metastasis and more recently there is evidence that they participate in tumor growth and angiogenic events. Matrix metalloproteinase 2 and 9 (MMP 2 and 9) belong to the gelatinases, a subgroup of MMPs, and have the capacity to degrade the triple helix type IV collagen of basal lamina of the basement membrane. With the present study, we tried to demonstrate the expression of MMP-9 immunohistochemically, comparatively in benign, premalignant and malignant lesions of the larynx. We studied 154 laryngeal lesions including 55 squamous cell carcinomas, 8 in situ carcinomas, 54 cases of dysplasia (of low and intermediate grade), 13 papillomas and 24 cases of keratosis. Overexpression of MMP 9 was observed in 74.4% and 50% in invasive and in situ squamous cell carcinomas respectively. In dysplastic cases, in papillomas and in keratoses the percentage of overexpression was 62.9%, 61.53% and 54.16% respectively and the expression of MMP-9 was significantly higher in invasive squamous cell carcinomas compared to dysplasias (p=0.000004). Also significantly higher was the expression of MMP-9 in dysplastic cases compared to papillomas (p=0.023). The MMP-9 expression was related neither to survival nor to the other available clinicopathological parameters (tumor size, grade, clinical stage, lymph node status and patient age). In conclusion, our study indicates that the expression of MMP-9 is up-regulated in a stepwise fashion, with two main steps, the first one, when a dysplastic lesion evolves and the next one, when the dysplasia progresses to invasive carcinoma.     

Mena, a new available marker in tumors of salivary glands?

Mena (mammalian Ena) is an actin regulatory protein involved in cell motility and adhesion. Based on its potential role in malignant transformation revealed in other organs, we analyzed the Mena expression in normal salivary glands (SG) and salivary tumors. Mena expression was determined in normal SG (n=10) and also benign (n=20) and malignant (n=35) lesions of SG. For the immunohistochemical staining we used the anti-Mena antibody. All normal SG and the benign lesions (10 pleomorphic adenomas, 10 Warthin's tumors) were Mena negative. Salivary duct carcinomas (n=5), carcinomas in pleomorphic adenoma (n=5), acinic cell carcinomas (n=5), squamous cell carcinomas (n=10) and high-grade mucoepidermoid carcinomas (n=2) were positive. The lymphomas (n=5) and low-grade mucoepidermoid carcinomas (n=1) were Mena negative. In one case the lymphoblastic cells stained positive for Mena. Some of the endothelial cells, in the peritumoral vessels, were Mena positive. To the best of our knowledge, this is the first study in the literature about Mena expression in salivary tumors. Our study suggests that Mena protein seems to play a role in malignant transformation and its intensity is correlated with the type and grade of tumor and also with vascular invasion. Its positivity in endothelial cells may suggest its potential role in tumor angiogenesis.     

Glycoprotein CD44 expression in benign, premalignant and malignant epithelial lesions of the larynx: an immunohistochemical study including correlation with Rb, p53, Ki-67 and PCNA.

CD44 is an integral membrane glycoprotein that has diverse functions in cell-cell and cell-substrate interactions. It has been suggested that it may be a determinant of metastatic and invasive behavior in carcinomas. The immunohistochemical expression of CD44 was examined in a series of 34 squamous cell carcinomas, 13 in situ carcinomas, 35 cases with various degrees of epithelial dysplasia, 10 papillomas and 17 cases of keratosis. We used the monoclonal mouse anti-human phagocytic glycoprotein-1 CD44 (clone DF 1485), on formalin-fixed, paraffin-embedded tissue. CD44 expression was correlated with the expression of Rb and p53 proteins, with the proliferative indices Ki-67 and PCNA as well as with conventional clinicopathological data. The mean value of CD44 expression was 78.84 in squamous cell carcinomas, 78.04 in situ carcinomas, 54.93 in dysplasia, 26.8 in papillomas and 24.97 in keratosis. There was no significant difference of CD44 expression between in situ and invasive carcinomas. However, a strong difference of reaction between carcinomas and the other cases was observed. CD44 expression was statistically higher in dysplastic lesions than the cases of keratosis (p < 0.0001) and papillomas (p = 0.01). In the group of invasive carcinomas, CD44 expression was statistically correlated with pRb (p = 0.011), while in preinvasive lesions it was correlated with PCNA (p = 0.016). The relationship with the degree of dysplasia or grade of carcinoma and p53 protein expression was insignificant. These observations suggest that CD44 expression may be involved in the multiple mechanism of the development and progression of laryngeal lesions and may help to predict the risk of transformation of the benign or precancerous lesions to cancer.     

CK5/6 in effusions: no difference between mesothelioma and pulmonary and nonpulmonary adenocarcinoma

OBJECTIVE: To test the performance of CK5/6 for the differentiation between mesothelioma, adenocarcinoma and benign mesothelia/proliferations in effusion cytology. STUDY DESIGN: CKS/6 immunocytochemistry was applied to ethanol-fixed cytospin preparations from 74 benign and malignant effusions. RESULTS: Reactivity was seen in 7 of 8 mesotheliomas and in 9 of 11 benign mesothelial proliferations but also in 11 of l7 pulmonary adenocarcinomas and in 12 of 31 adenocarcinomas of nonpulmonary origin. Reactivity was also found in 3 of 5 non-small cell lung carcinomas and 1 of 1 squamous carcinoma. CONCLUSION: CK5/6 reactivity was found in a considerable proportion of metastatic adenocarcinomas of pulmonary and nonpulmonary origin. The high reactivity rate in pulmonary adenocarcinomas disagrees with the results obtained with histologic sections from solid tumor tissue, and CK5/6 seems to be of very limited value as an additional marker in effusion cytology.     

The evaluation of human papillomavirus and p53 gene mutation in benign and malignant conjunctiva and eyelid lesions

Papillomas and squamous cell carcinomas are the most common conjunctival and eyelid lesions. The etiology is still unclear and recently human papillomavirus infection and p53 gene mutation have been taken into consideration. The aim of our study was the evaluation of HPV DNApresence and p53 gene mutation in 45 benign and 38 malignant squamous lesions of the conjunctiva and eyelid. For HPV detection PCR-RFLP and immunohistochemical reaction were used; for p53 gene mutation PCR-SSCP was used. Only 8.8% papillomas, 9.1% squamous cell cancers and 3.7% basal cell cancers (using PCR-RFLP method) and 26.6% papillomas, 7.4% squamous cell cancers and 9.1% basal cell cancers (using immunohisto-chemical reaction) were HPV positive. p53 gene mutation was evaluated in 24.4% papillomas, 54.5% squamous cell cancers and 22.2% basal cell cancers; most commonly in 6 and 7 exon. Human papillomavirus infection, opposite to p53 gene mutation, is not a significant etiological factor of the benign and malignant conjunctival and eyelid lesions development.     

Use of specimen mammography-guided FNA (fine-needle aspirates) for flow cytometric multiple marker analysis and immunophenotyping in breast cancer

A pilot study of a novel translational research method to simultaneously assay multiple molecular markers and DNA in fine-needle aspirates (FNA) of mammographically detected breast lesions is described. Specimen mammography-guided 20-gauge FNAs obtained from 86 lesions and 22 areas of normal tissue were analyzed by multiparameter flow cytometry for DNA content, her2/neu, transforming growth factor alpha (TGF alpha), and the epithelial marker cytokeratin (CK) simultaneously. Epithelial cell her2/neu positivity was detected in 12 of 44 (27%) of invasive ductal carcinomas and 3 of 9 (33%) ductal carcinoma in situ (DCIS), 10 of 30 (33%) benign lesions, and 4 of 22 (18%) normal tissue aspirates. All lesions and normal tissue showed a similar positive rate for TGFalpha ranging from 61 to 76%. The CK(+)TGF alpha(-)her2/neu(+) immunophenotype was more frequently positive in aneuploid tumors (22%) than all other lesions (7%) (P < 0.05). Specimen mammography-guided FNAs provide fresh cells for flow cytometric multiple marker analysis and immunophenotyping of clinically occult breast lesions and normal tissue.     

Keratin polypeptide distribution in benign and malignant breast tumors: subdivision of ductal carcinomas using monoclonal antibodies

Monoclonal antibodies which recognize one or only a few keratin polypeptides have been used to study the distribution of different keratins in benign and malignant breast lesions by immunocytochemical methods. Seven monoclonal antibodies which recognized either different keratin polypeptides by immunoblotting techniques, or identified different epithelial cell types in complex tissues were used. In two mastopathies and three fibroadenomas the antibody lu5 stained luminal cells as well as myoepithelial cells. In contrast the antibodies CK7, Troma 1, CK2 and KA4 labeled only luminal cells, whereas antibody CKB1 decorated only myoepithelial cells. All 15 ductal carcinomas showed a uniform staining of tumor cells with the antibodies Troma 1, CK2, KA4 and lu5. The antibody CK7 also stained all ductal carcinomas, but in two specimens the staining was heterogeneous. The antibody CKB1 decorated only the pre-existing myoepithelial cells in 11 of 12 ductal carcinomas but in the remaining specimen the tumor cells were also strongly positive. Tumor cells in lobular carcinomas were labeled by antibodies CK7, Troma 1, CK2, KA4, bu not by CKB1. The antibody CKS1 showed no staining of any of the benign and malignant breast lesions.     

Expression of retinoblastoma gene product in respiratory epithelium and sinonasal neoplasms: relationship with p16 and cyclin D1 expression

Transition from G1 to S phase of the cell cycle is mediated by interactions between the Retinoblastoma gene product (pRb), p16, and cyclin D1. To determine the expression of these proteins in the sinonasal mucosa immunohistochemistry was carried out on archived tissue sections from 46 patients (37 men, 9 women, age range 17 to 82 years, median 55 years). Nuclear immunostaining for these proteins was assessed and the expression rates (percentages of immunoreactive nuclei) in normal respiratory epithelium, inverted sinonasal papillomas, cylindrical (oncocytic) sinonasal papillomas, and squamous cell carcinomas were compared. Normal respiratory epithelium showed significantly higher pRb expression in surface cells compared to basal cells (p < 0.05). In contrast, abundant pRb expression in surface and basal cells was detected in columnar differentiation in sinonasal papillomas and adjacent mucosa. Cuboidal and squamous metaplasia in inverted papillomas showed significantly reduced pRb expression in surface cells compared to columnar epithelium in inverted papillomas (p < 0.05, respectively). Expression of p16 was detected in all epithelial cell layers of normal respiratory epithelium, sinonasal papillomas, and adjacent mucosa. Cuboidal and squamous metaplasia in inverted papillomas showed increased p16 expression in surface cells compared to columnar epithelium in inverted papillomas (p < 0.05 between squamous metaplasia and columnar epithelium). Sinonasal squamous cell carcinomas showed the coexpression of pRb and p16. Expression rates of cyclin D1 higher than 10% were detected only in invasive carcinomas but not in carcinoma in situ, sinonasal papillomas or respiratory epithelium. Conclusively, pRb expression accompanies terminal differentiation in columnar surface cells. Expression of pRb in proliferating basal cells is present in sinonasal papillomas and adjacent mucosa but not in normal respiratory epithelium. Cuboidal and squamous metaplasia in inverted papillomas involves downregulation of pRb expression along with increased p16 expression in surface cells. Sinonasal squamous cell carcinomas coexpress pRb and p16. Overexpression of cyclin D1 in sinonasal lesions is confined to invasive squamous cell carcinomas.     

Neutrophil gelatinase-associated lipocalin (NGAL) immunohistochemical expression in follicular cell-derived thyroid tumors: a novel diagnostic tool?

Discrimination of follicular cell-derived benign and malignant tumors of the thyroid is one of the major problems encountered in surgical pathology. In the present study, we evaluated the immunohistochemical expression of NGAL, an iron-binding protein involved in the infiltrative potential of cancer cells, in a cohort of tumors including 8 follicular adenomas (FA), 2 Hurthle cell adenomas (HA), 2 atypical adenomas (AA), 8 minimally invasive follicular carcinomas (MIFC), 9 widely invasive follicular carcinomas (WIFC), 3 Hurthle cell carcinomas (HC) and 8 papillary carcinomas (PC) with 5 follicular-variant PC (FVPC) and 3 not otherwise specified (PC-NOS). Our goal was to test whether evaluation of NGAL immunoexpression may be of use in the differential diagnosis of benign and malignant thyroid neoplasias. 92% of benign tumors (specificity) were negative for NGAL, whereby NGAL immuno-expression was found in 82% (sensitivity) of malignant tumors, and, specifically, in 100% of MIFC, in 87% of WIFC, in 100% of HC, in 80% of FVPC. None of the PC-NOS displayed NGAL staining. When only tumors with a follicular architecture were considered, NGAL specificity for malignant lesions was 92%; sensitivity, positive predictive value and negative predictive value were 92%, 96% and 85%. Diagnostic accuracy of NGAL expression in the differential diagnosis between benign and malignant follicular tumors was 92%. In conclusion, NGAL protein seems to represent a marker of malignant follicular cell-derived thyroid tumors, and especially of those with follicular architecture. Hence assessment of its expression might be of use with respect to differential diagnosis from follicular benign neoplasias.     

The impact of operative approach on outcome of surgery for gastro-oesophageal tumours

Background

Caveolin-1 is thought to have an important impact on both signal transduction and mediation of intracellular processes. Furthermore, it has been suggested that Caveolin-1 may contribute to certain steps of carcinogenesis in various types of cancer. We examined the potential clinical relevance of Caveolin-1 in normal, benign and malignant breast tissue specimens.

Methods

Using tissue microarray (TMA) technology cases of invasive breast cancer, DCIS, benign breast disease (i.e. fibroadenoma, sclerosing adenosis, ductal hyperplasia and radial scar) and normal breast tissue were evaluated for Caveolin-1 expression. Immunohistochemical staining with an anti-Caveolin-1-antibody was performed. Staining intensity was quantified semiquantitatively. In invasive lesions staining results were correlated with clinical and pathological data.

Results

No Caveolin-1 expression was observed in epithelial cells of normal breast tissue (n = 5), benign breast disease (n = 295) and DCIS (n = 108). However, Caveolin-1 expression was found in 32 of 109 cases of invasive breast carcinomas (29.4%). Caveolin-1 expression in invasive breast cancer could neither be correlated with survival parameters such as overall or disease-free survival nor with established clinical and pathological markers.

Conclusion

In this study we demonstrated expression of Caveolin-1 in one third of invasive breast cancers. A significant increase in Caveolin-1 expression was observed comparing invasive breast cancer to both benign breast tissue and non-invasive breast cancer. Since inhibitors of Caveolin-1 signalling are available, targeting Caveolin-1 in breast cancer may represent a potential option for future breast cancer treatment.     

The conversion of mouse skin squamous cell carcinomas to spindle cell carcinomas is a recessive event

Squamous carcinomas of both human and rodent origin can undergo a transition to a more invasive, metastatic phenotype involving reorganization of the cytoskeleton, loss of cell adhesion molecules such as E-cadherin and acquisition of a fibroblastoid or spindle cell morphology. We have developed a series of cell lines from mouse skin tumors which represent different stages of carcinogenesis, including benign papillomas, and clonally related squamous and spindle carcinomas derived from the same primary tumor. Some spindle cells continue to express keratins, but with a poorly organized keratin filament network, whereas in others no keratin expression is detectable. All of the spindle cells lack expression of the cell adhesion molecule E-cadherin and the desmosomal component desmoplakin. Loss of these cell surface proteins therefore appears to precede the destabilization of the keratin network. At the genetic level, it is not known whether such changes involve activation of dominantly acting oncogenes or loss of a suppressor function which controls epithelial differentiation. To examine this question, we have carried out a series of fusion experiments between a highly malignant mouse skin spindle cell carcinoma and cell lines derived from premalignant or malignant mouse skin tumors, including both squamous and spindle carcinoma variants. The results show that the spindle cell phenotype as determined by cell morphology and lack of expression of keratin, E-cadherin, and desmoplakin proteins, is recessive in all hybrids with squamous cells. The hybrids expressed all of these differentiation markers, and showed suppression of tumorigenicity to a variable level dependent upon the tumorigenic properties of the less malignant fusion partner. Our results suggest that acquisition of the spindle cell phenotype involves functional loss of a gene(s) which controls epithelial differentiation.     

Proliferating activity in oral dysplastic leasions and squamous cell carcinomas

The aim of the study was the quantitative analysis of AgNORs in oral squamous cell carcinomas as well as in dysplastic epithelial changes accompanied and not accompanied by oral squamous cell carcinomas. AgNOR proteins were visualized in histological slides using silver impregnation technique according to D. Ploton. In each sample 100 cell nuclei were assessed. The study used 54 cases of proliferating oral epithelial changes divided into 3 groups: group I consisting of 13 cases of dysplastic lesions not accompanied by oral squamous cell carcinomas; group II (a total of 18 cases) containing dysplastic lesions situated in the vicinity of oral carcinomas and group III (23 cases) with oral squamous cell carcinomas. Statistically significant differences were found between groups with mild dysplasia and groups with severe dysplasia as well as squamous cell carcinomas. Statistical analysis did not show any differences in the number of AgNORs between squamous cell carcinomas and epithelial lesions with severe dysplasia. Our results demonstrate that the analysis of AgNORs expression can serve only as an additional parameter to evaluate the potential of malignant transformation.     

Different expression of cyclooxygenase-2 (COX-2) in selected nonmelanocytic human cutaneous lesions

The aim of our study was to elucidate the possible involvement of COX-2 in the development and/or progression of nonmelanocytic skin lesions. To evaluate the usefulness of that enzyme as a potential molecular marker, we examined the intensity and spatial distribution of COX-2 expression in selected types of such tumors using the same immunohistochemical procedure as in our earlier studies of melanocytic cancers. We examined 20 benign epithelial lesions, 11 precancerous lesions, 21 basal cell carcinomas (BCC), 14 squamous cell carcinomas (SCC) and eight fibromas. The levels of COX-2 expression detected in benign lesions and in normal skin were comparable. Elevated expression of this protein may play a role in the development of SCC, as indicated by strong immunostaining both in SCCs and precancerous lesions. Significantly stronger staining in SCCs compared to BCCs may indicate a role of COX-2 in cancer malignancy and serve as an indicator useful for differential diagnostics of the two types of cancer. Strong staining in all skin layers of SCC may help in detecting cancer cells infiltrating surrounding skin layers.     

Diagnostic utility of galectin-3 in aspirates of thyroid follicular lesions

OBJECTIVE: To investigate the expression of galectin-3 in various thyroid follicular lesions, including diffuse hyperplasia, nodular hyperplasia, and benign and malignant follicular neoplasms, to clarify the diagnostic utility of galectin-3 in aspirates of follicular lesions. STUDY DESIGN: A total of 146 follicular lesions diagnosed cytologically, obtained from patients who had undergone thyroidectomy for either benign or malignant nodules, were evaluated using Papanicolaou-stained slides and cell blocks with galectin-3 immunostaining. We primarily categorized the aspirated specimens as benign, indeterminate or suspicious for a follicular neoplasm based on cellularity, architectural arrangement of the follicular cells and presence or absence of colloid. Galectin-3 immunostaining was evaluated according to the proportion and intensity of positively stained cells. Cytologic diagnoses were correlated with the results of galectin-3 and categorized into 3 groups (benign, indeterminate for malignancy, suspicious for malignancy) and compared with the corresponding histologic diagnoses. RESULTS: When the histologic diagnoses were compared with the cytologic diagnoses, the accuracy in the distinction between benign and malignant cases was 79.5% except for 8 cytologically and 3 histologically indeterminate cases. Except for 11 indeterminate cases, there were 18 (12.3%) discrepant cases. False positive cases included 8 of 62 (12.9%) nodular hyperplasias and 1 of 42 (2.4%) follicular adenomas. Of 9 false negative cases, 4 minimally invasive carcinomas and 2 widely invasive carcinomas were included. Three follicular tumors of uncertain malignant potential were cytologically categorized as malignant, and all cases showed positivity for galectin-3. CONCLUSION: Galectin-3 could be used as a useful supplementary marker for cytologic diagnosis, although it was not an absolute marker in determining whether a lesion was benign or malignant.