Preferentially expressed antigen in melanoma expression in nonmelanoma skin cancers and melanocytes in surrounding skin.

BACKGROUND: Immunohistochemistry for preferentially expressed antigen in melanoma (PRAME) has been studied in melanocytic lesions but not nonmelanoma skin cancers (NMSCs). This study evaluated PRAME expression in NMSCs and dermoepidermal junction (DEJ) melanocytes in the surrounding skin. METHODS: Ninety-nine NMSCs were studied: 23 Merkel cell carcinomas (MCCs), 25 well to poorly differentiated squamous cell carcinomas (SCCs), 14 basal cell carcinomas (BCCs), five basosquamous carcinomas, four sebaceous carcinomas, ten atypical fibroxanthomas, 11 dermatofibrosarcoma protuberans, and seven leiomyosarcomas. Staining quality was considered low or high intensity. Staining quantity was reported as negative 0%, 1% to 24%, 25% to 50%, and >50%. DEJ melanocyte PRAME expression was recorded. RESULTS: Forty-eight percent of NMSCs showed PRAME expression, mostly low intensity in fewer than 25% of cells. High-intensity expression was noted in one poorly differentiated SCC, six BCCs, and seven MCCs. Only MCCs showed expression in greater than 25% of tumor cells. Focal DEJ melanocytes expressed high-intensity PRAME in 18% of cases, most commonly SCCs (11/23). CONCLUSIONS: PRAME is negative or expressed with low intensity in a small percentage of NMSCs, with the exception of some MCC showing high-intensity and diffuse staining. Focal DEJ melanocytes showed high-intensity PRAME reactivity in the skin surrounding some NMSCs.

Toll-Like Receptor 7 Staining in Malignant Epithelial Tumors.

BACKGROUND: As important players of the innate immune system, Toll-like receptors (TLRs) and their role for tumorigenesis have been in the focus of research. In particular TLR7 is an interesting candidate, as TLR7 agonists are broadly used for the treatment of cutaneous tumors. However, data addressing the baseline expression of TLR7 in both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) on the protein level are lacking, while on the genomic level significantly elevated expression of TLR7 in SCC but not in BCC has been demonstrated. AIM: Our aim was to characterize the immunohistochemical staining pattern of TLR7 in SCC and BCC. Besides, we aimed to clarify if, in case of different TLR7 expression between SCC and BCC, TLR7 expression would help to define basosquamous carcinoma (BSC), a tumor entity sharing characteristics of both SCC and BCC. METHODS: We examined histopathological samples from 23 BCC, 4 BSC, and 24 SCC and characterized the expression of TLR7 by immunohistochemistry and immunofluorescence. RESULTS: We found that TLR7 was not expressed by the tumor tissue of SCC, BCC, and BSC, but by inflammatory cells located within the tumoral and/or peritumoral tissue. Whereas the overall expression of TLR7 did not differ between BCC and SCC (30.4% vs. 45.8%, respectively), we found that within the group of SCC, the well-differentiated SCC showed strong tumoral and/or peritumoral immunocellular TLR7 reactivity in contrast to the poorly differentiated SCC (73.33% vs. 11.1%, respectively). Besides, immunofluorescence double staining revealed the expression of TLR7 in immune cells closely interacting with T cells and natural killer cells. CONCLUSIONS: In contrast to genomic data, we did not find a general difference between baseline TLR7 expression of SCC and BCC on the protein level. Nevertheless, the expression of TLR7 by the inflammatory infiltrate associated with SCC may correlate with the degree of differentiation of SCC possibly indicating better outcome.

Basaloid squamous cell carcinoma of the conjunctiva.

Basaloid squamous cell carcinoma is a distinct variant of squamous cell carcinoma, and it is more aggressive and has a poorer prognosis than conventional squamous cell carcinoma. Basaloid squamous cell carcinoma has been reported to arise from many organs, mainly in the upper aerodigestive tract. Herein, the authors present a 77-year-old woman with a basaloid squamous cell carcinoma over her limbal conjunctiva in the OD.

Angiogenin expression in head and neck basaloid and conventional squamous cell carcinoma: a site- and stage-matched comparison.

BACKGROUND: Basaloid squamous cell carcinoma is an uncommon variant of squamous cell carcinoma (SCC). Angiogenin (ANG), a member of the ribonuclease super-family, is essential to tumor angiogenesis, but has also been implicated in tumor consolidation and proliferation. METHODS: ANG expression was first investigated in 12 head and neck basaloid squamous cell carcinomas (HNBSCCs) and compared with a control group of 24 site- and stage-matched conventional SCCs to establish whether the supposedly more aggressive biological behavior of HNBSCCs might be ANG-related. RESULTS: No significant differences were found between HNBSCCs, and SCCs in terms of recurrence, disease-free survival (DFS), or overall survival rates. In HNBSCC, we identified a trend toward a significant inverse correlation between endothelial ANG expression and DFS (statistical trend, P = 0.08). Endothelial ANG expression did not differ significantly in HNBSCCs and SCCs. A high ANG expression in carcinoma cells was directly associated with pT in both the HNBSCC (P = 0.04) and the SCC (statistical trend, P = 0.07) groups. ANG expression in carcinoma cells was significantly lower in HNBSCCs than in SCCs (P = 0.005). CONCLUSIONS: All the biological mechanisms investigated to date, including ANG-mediated angiogenesis or cell proliferation, have failed to confirm that HNBSCCs have a more aggressive behavior than matched SCC.

Differential expression of glucocorticoid receptor in carcinomas of the human digestive system.

AIMS: To investigate the in situ expression profile of glucocorticoid receptor (GR) in normal and carcinomatous tissues of the human digestive system. METHODS AND RESULTS: Specimens from 306 carcinomas of the human digestive tract were assayed for the expression of GR by immunohistochemistry. GR expression was strong in oesophageal squamous epithelia, pancreatic islet cells and hepatocytes, but generally weak or negative in non-squamous epithelia. Consistently, GR expression was found in a high percentage of oesophageal squamous cell carcinomas (SCC) (98.1%) and hepatocellular carcinomas (HCC) (92.9%), but rarely in gastric adenocarcinomas (7.4%) and not at all in colorectal adenocarcinomas (0%). Dexamethasone (DEX) was found to confer chemoresistance in oesophageal SCC and HCC cells, suggesting that GR expression may be biologically important in some GR-expressing carcinomas. CONCLUSIONS: Distribution of GR expression is markedly diverse among tissues of the human digestive system. The general lack of GR in adenocarcinomas contrasts with the high percentage of SCCs and HCCs expressing GR, and, along with the generation of chemoresistance by DEX, warrants prospective study of the effects of steroids on these cancers.

Decreased expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor in basal cell carcinomas.

Thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor is associated with tumor angiogenesis. We evaluated the TP mRNA and protein expression in basal cell carcinomas (BCC) and in various skin tumors including numerous BCC histological simulants. Immunohistochemistry was performed on 99 paraffin sections of formalin-fixed skin tumors using monoclonal antibodies (mAb) against TP. TP mRNA levels were measured by real time RT-PCR in whole BCCs (wBCC) and laser capture microdissected (LCM) BCC tumor cells. TP immunostaining was negative in all BCC variants and in most of the benign trichogeneic tumors studied. By contrast, TP was constantly immunodetected in actinic keratosis (AK), squamous cell carcinomas (SCC), syringomatous carcinomas (SC), basosquamous carcinomas (BSC) and melanomas. TP mRNA levels were low and statistically not different in wBCC and normal skin but were strongly downregulated in LCM-BCC as compared with LCM-normal epidermis. We concluded that (i) anti-TP mAb is an useful marker to differentiate BCC from AK, SCC, BSC and SC but not from trichoblastic tumors, (ii) the lack of TP protein expression in BCC tumoral cells is linked to transcriptional regulatory mechanisms, (iii) the low TP mRNA levels in whole BCC may be related to the low intra-tumoral microvessel density, the slow growth and the very low metastatic potential of these tumors.

A clinicopathologic study on basaloid squamous cell carcinoma in the oral and maxillofacial region.

Basaloid squamous cell carcinoma (BSCC) is a rare distinct variant of squamous cell carcinoma (SCC). To investigate its clinical behavior and prognosis, 15 patients with BSCC in the oral and maxillofacial region were clinically analyzed and compared with 15 patients with conventional SCC matched for site, stage, gender and age. To understand its immunohistochemical features, sections for cytokeratin AE1/AE3, CK 13. CK 7, CK 8, proliferating cell nuclear antigen (PCNA) and p53 were reviewed from 12 patients with BSCC. The rate of cervical lymph node metastasis of BSCC was as high as 67% and that of distant metastasis 13%. The tumor recurrence rate was 33% and the 3-year and 5-year survival rates were 53% and 32%, respectively. For conventional SCC, the cervical lymph node metastasis rate was 27%, that of distant metastasis 7%, tumor recurrence rate was 33%, and 3-year and 5-year survival rates were 80% and 70%, respectively. In most BSCC patients (10/12) the PCNA index was over 50%. Twelve BSCC patients were diagnosed with grade II or III conventional SCC when the original records of the primary diagnosis for the 15 patients with BSCC were reviewed. The biological behavior and prognosis of BSCC are similar to those of poorly differentiated SCC.

Expression of glucose transporter protein-1 (Glut-1) in ocular surface squamous neoplasia.

PURPOSE: To examine the expression of glucose transporter protein-1 (GLUT-1) in ocular surface squamous neoplasia and to study its relationship with degree of neoplasia and cell proliferation index (Ki-67 labeling index). METHODS: Twelve cases diagnosed as ocular surface squamous neoplasia (4 invasive and 8 intraepithelial tumors) at Inonu University Faculty of Medicine, Department of Pathology, were included in this study. There were 3 squamous cell carcinomas, 1 basosquamous cell carcinoma, and 8 conjunctival intraepithelial neoplasms. Immunohistochemically, GLUT-1 and Ki-67 antibody staining were performed. RESULTS: GLUT-1 membranous immunoreactivity was seen in all tumors except in 1 case. GLUT-1 immunostaining was observed in all layers of the neoplastic epithelium of squamous cell carcinoma. Intense staining for GLUT-1 was determined in the upper two thirds of the severe dysplastic squamous epithelium. Although immunoreactivity for Ki-67 nuclear antigen was present throughout the epithelium, it was higher in the lower two thirds. Ki-67 labeling index ranged between 6% and 80%, and the mean value was 35% for invasive tumors and 20% for intraepithelial tumors. CONCLUSIONS: Marked GLUT-1 and Ki-67 immunoreactive cells throughout the neoplastic epithelium of ocular surface squamous neoplasia were observed. In most cases, it was observed that GLUT-1 expression was severe in cases having >10% Ki-67 labeling index. These findings indicate that glucose uptake was increased in dysplastic cells, especially by GLUT-1. To our knowledge, this is the first study on the subject in the literature, and further studies with more cases are needed with GLUT-1 and other GLUT members.

Sarcomatoid carcinoma with a predominant basaloid squamous carcinoma component: the first report of an unusual biphasic tumor of the ureter.

Malignant tumors of the ureter that display biphasic patterns are very rare; they include carcinosarcomas, sarcomatoid carcinomas and carcinomas with pseudosarcomatous stroma. Although the distinction between carcinosarcomas and sarcomatoid carcinomas has been extensively discussed in the past, the recent World Health Organization classification of urinary tract tumors (2004) does not distinguish the two lesions and use the term sarcomatoid carcinoma to represent these biphasic tumors. The epithelial components of previously reported ureteral biphasic tumors comprise transitional cell carcinoma, squamous cell carcinoma, carcinoma in situ, small cell carcinoma and adenocarcinoma. In this paper, we report the first case of sarcomatoid carcinoma of the ureter with a predominant basaloid squamous carcinoma component. A 63-year-old man who had developed asymptomatic gross hematuria was diagnosed with a right ureteral tumor and underwent a right nephroureterectomy. Macroscopic examination of the excised tumor revealed a polypoid mass. Histopathologic examination exposed a tumor with malignant epithelial and sarcomatous components. The malignant epithelial component was predominantly composed of basaloid squamous carcinoma, and the sarcomatous component was mostly composed of undifferentiated spindle cells. A small focus of a chondrosarcomatous component was present. There were also transitional zones between the two components. In addition, the spindle cells of the sarcomatous component were partially positive for cytokeratin 7. We believe that the findings of this case study will increase the morphological diversity used for diagnosing malignant tumors of the ureter.

High nuclear expression of the apoptosis inhibitor protein survivin is associated with disease recurrence and poor prognosis in laryngeal basaloid squamous cell carcinoma.

CONCLUSION: Nuclear expression of survivin should be studied as a promising marker of higher-risk laryngeal basaloid squamous cell carcinomas (BSCCs), which can then be treated more aggressively and followed more closely. OBJECTIVE: BSCC is an uncommon bimorphic variant of SCC. The hypothesized greater aggressiveness and poorer prognosis of head and neck BSCC compared to SCC are still under debate. The regulation of apoptotic cell death has a profound effect on the pathogenesis and progression of malignancies. Survivin is the smallest member of the inhibitor of apoptosis gene family. The aim of this study was to investigate for the first time the expression of the inhibitor of apoptosis protein survivin in laryngeal BSCCs and their neck lymph node metastases and to compare the results with those obtained with conventional SCCs. MATERIAL AND METHODS: Immunoreactivity to survivin was determined in nine laryngeal BSCCs and nine site- and stage-matched SCCs. RESULTS: A nuclear subcellular localization of survivin dominated in both primary laryngeal BSCCs and SCCs and in their lymph node metastases. There was no significant difference in mean survivin expression between primary laryngeal BSCCs (25.1%) and SCCs (25.6%) (p=0.86). Nuclear survivin expression was significantly higher in BSCCs associated with disease recurrence and poor prognosis (p=0.02).

Basaloid squamous carcinoma of the anal canal with an adenoid cystic pattern: histologic and immunohistochemical reappraisal of an unusual variant.

Two cases of a distinctive variety of basaloid squamous carcinoma (BSC) of the anal canal are described. Both occurred in female patients who presented with bleeding per rectum. Histologic evaluation of the tumors showed lobules and aggregates of medium-sized basaloid cells with distinctive peripheral palisading and focal areas of central, comedo-necrosis. Accompanying dysplasia of the overlying squamous mucosa was absent. However, the microscopic pattern was dominated by the presence of eosinophilic, hyaline, paucicellular basement membrane-like material around and within tumor nests. This appearance together with microcystic spaces simulated that of an adenoid cystic carcinoma. Immunohistochemistry of the tumors revealed the following profile: CK7, CK5/CK6, 34betaE12 positive, CK14 focally positive but CK20 negative. The following were all negative: EMA, CEA, smooth muscle and muscle-specific actin, calponin, and S-100. The tumor cells exhibited diffuse nuclear positivity with p63. The eosinophilic basement membrane hyaline material was positive for collagen type IV and also for laminin. BSC of the anal canal with an adenoid cystic pattern is an infrequently encountered and reported variant, although it is seen more often in the aerodigestive tract. There may be an increased propensity for BSC with an adenoid cystic pattern to metastasize to the liver, but the number of cases encountered are too small to be definitive. The histologic differential diagnosis is true salivary gland-type adenoid cystic carcinoma and basal cell adenocarcinoma. Immunohistochemistry and awareness of this unusual pattern of BSC will facilitate the correct diagnosis being reached.

Endoglin (CD105) expression in head and neck basaloid squamous cell carcinoma.

CONCLUSIONS: This comparison of neo-angiogenesis performed by analysing CD105 expression seems to suggest that the biological behaviour of head and neck BSCCs is similar to that of site- and stage-matched conventional SCCs. OBJECTIVE: Basaloid squamous cell carcinoma (BSCC) is an uncommon, high-grade biomorphic variant of SCC with a predilection for the head and neck region. It is a matter of controversy whether the biological and clinical behaviour of BSCC is more aggressive than that of SCC. Angiogenesis is essential for tumour growth. It has been established that endothelial cells of tumour-associated neovasculature proliferate more rapidly than endothelial cells of normal tissue. Endoglin (CD105) has been shown to be a useful marker for identifying proliferating endothelium involved in tumour angiogenesis. The aim of this study was to investigate the expression of CD105 in head and neck BSCCs and to compare it with that in SCCs. MATERIAL AND METHODS: Nine head and neck BSCCs (five cases in the larynx, three in the tongue and one in the tonsil) were considered. A group of nine site- and stage-matched SCCs was examined simultaneously. For each sample, CD105 reactivity was evaluated immunohistochemically. The mean area fraction (percentage of fields occupied by vessels), the percentage of vessel-presenting fields and the vessel density were considered. RESULTS: The median values of the mean area fraction were 1.01% and 0.9% in BSCCs and SCCs, respectively. The median values of the percentage of vessel-presenting fields were 57.5% and 46.67% in BSCCs and SCCs, respectively. The median values of vessel density were 2.07% and 1.58% in BSCCs and SCCs, respectively. Statistical analysis did not disclose any significant differences between BSCCs and SCCs for any of the above-mentioned parameters.

Basosquamous carcinoma: is it an aggressive tumor?

Basosquamous carcinoma is a rare cutaneous tumour that is considered an aggressive type of basal cell carcinoma with an increased risk of recurrence and metastases. This impression has been perpetuated in the literature, despite limited scientific data and conflicting results of some authors. This present study was aimed to evaluate the clinical-pathological features of this tumour and follow-up of a series of basosquamous carcinoma. Basosquamous carcinoma patients who underwent surgical excision between January 2000 and February 2012 were analyzed retrospectively. Their medical files were reviewed and the corresponding routinely stained sections (with hematoxylin-eosin) were re-evaluated by two pathologists. Thirty-five patients with basosquamous carcinoma were operated on in this period. Most tumurs were located in the head and neck area (94%), and the mean age of the patients was 69.8 years. Margin involvements were seen in 11 patients (31.4%) and all of them underwent re-excision. There was only one local recurrence. There was neither regional lymph node nor distant metastasis in this series. The recurrence rate of basosquamous carcinoma is found as 4%, lower than that of most other similar studies. Further pathologic studies are needed to better classify basosquamous carcinoma and to increase consistency between the results of studies. Surgical excision and regular follow-up are considered as the treatment of choice.

Glycoprotein metabolism in skin cancer: synthesis, pool size, and partial characterization of glycoproteins in the rat basosquamous cell carcinoma.

Uptake of fucose, glucosamine, galactose, and mannose and the incorporation of these sugars into glycoconjugates have been quantified in a model epithelial tumor, the basosquamous cell carcinoma of the rat. Following isolation of glycoprotein and papain digestion, the fucosylated glycopeptides were fractionated according to molecular weight (Mr) and by affinity chromatography. Analysis of cellular material revealed a 2- to 3-fold reduction in the proportion of high-Mr fucopeptides synthesized by the tumor compared with normal epidermis, accompanied by a profound block in the incorporation of galactose into glycoconjugates. Parallel investigation of carbohydrate removed from the cell surface with trypsin or spontaneously shed into the medium indicated a striking decrease in the total release of fucopeptides from the tumor; the Mr was (respectively) normal or increased. Thus the fucopeptide abnormality appears to be accounted for almost entirely by a shift toward accumulation of low-Mr material at internal locations within the cell.

Spindle cell epithelioma, the so-called mixed tumor of the vagina. A clinicopathologic, immunohistochemical, and ultrastructural analysis of 28 cases.

A total of 28 examples of vaginal mixed tumors, a circumscribed tumor composed predominantly of spindle cells, but often admixed with minor glandular, and focal areas of squamous differentiation along with localized hyaline globules, were evaluated. In addition to the clinicopathologic correlation with light microscopy, 10 cases were analyzed immunohistochemically by a panel of antibodies for keratin, smooth muscle actin, S-100 protein, and glial fibrillary acidic protein; five cases were also evaluated for estrogen and progesterone receptors. Ultrastructural analysis was performed on two tumors. The results indicate an epithelial differentiation in the predominating spindle cells based upon an intense immunoreaction with cytokeratin in nine of 10 cases and the presence of tonofilaments and desmosomes at the ultrastructural level. Contrary to mixed tumors of salivary gland and breast origin, no evidence of a myoepithelial differentiation was identified in these tumors. The name vaginal spindle cell epithelioma is proposed for these neoplasms as being more descriptive of the true nature of these tumors.

Basaloid squamous cell carcinoma of the maxilla.

The study reports the first case of basaloid squamous cell carcinoma (BSCC) involving both the oral mucosa and the tuberosity area of the maxilla. The tumour showed many histological similarities to cases previously reported, though mitoses were not frequent. The immunoreactivity for cytokeratin, S-100, vimentin, Ki-67, p53, c-erbB-2 and bcl-2 was also investigated. Immunostaining for the bcl-2 protein showed a high extent of positive cells, although only a moderate staining intensity. Staining for c-erbB-2 was negative. The pathological findings and the immunoreactivity may indicate that BSCC is not as high a grade carcinoma as previously suggested. Additional studies are thus clearly needed to confirm or reject this impression.

BerEp4, cytokeratin 14, and cytokeratin 17 immunohistochemical staining aid in differentiation of basaloid squamous cell carcinoma from basal cell carcinoma with squamous metaplasia.

CONTEXT: Basaloid squamous cell carcinoma (bSCC) is an uncommon variant of squamous cell carcinoma, which may overlap histologically with basal cell carcinoma with squamous metaplasia (BCCm). OBJECTIVE: To aid in the differentiation of these neoplasms using immunohistochemical staining because of the worse prognosis associated with bSCC. DESIGN: Using immunohistochemical techniques, we investigated BerEp4, cytokeratin 17 (CK17), and cytokeratin 14 (CK14) protein expression in 25 cases of bSCC (8 cutaneous [32%], 12 aerodigestive tract [48%], and 5 lymph node metastases [20%]) and 43 cases of BCCm (39 cutaneous [91%], and 4 metastases [9%]). An immunoreactivity score was assigned using the percentage of tumor cells staining and the pattern of expression. Interobserver agreement for 2 independent pathologists was assessed using a κ coefficient. RESULTS: The mean percentage of staining was significantly higher in BCCm, compared with bSCC (BerEp4, P = .006; CK17, P < .001; CK14, P < .001; unpaired t test), with 58% of BCCm cases (25 of 43) displaying diffuse staining for all markers, and nearly all (98%; 42 of 43) displaying diffuse staining for CK17 and CK14. In contrast, no bSCC cases (0%) displayed diffuse staining for all 3 markers, and only 8% (2 of 25) displayed diffuse staining for CK17 and CK14. High interobserver agreement was determined. CONCLUSIONS: BerEp4 alone is unreliable for differentiation between BCCm and bSCC, and the addition of either CK14 or CK17 will augment the sensitivity and negative predictive value of BerEp4 staining in BCCm and bSCC diagnosis.

Ber-EP4, CK1, CK7 and CK14 are useful markers for basaloid squamous carcinoma: a study of 45 cases.

Diagnosis of basaloid squamous carcinoma (BSCC) currently relies mainly on histological criteria, with variable immunohistochemical results reported in small series. We explored the use of a battery of immunohistochemical stains to elucidate this diagnosis on 45 cases of BSCC. To further elucidate the immunohistochemical profile of BSCC, to explore potential genetic pathways of malignant transformation using proliferation markers, and to investigate a possible link with Human Papillomavirus (HPV). Forty-five cases of BSCC and 34 site-matched cases of squamous cell carcinoma (SCC) were obtained from the archives of the pathology department at our institution. Extensive literature review was undertaken utilizing Medline. Ber-EP4 is a useful diagnostic marker for BSCC, positive in 82% (37/45) of the cases and in 68% (23/34) of SCC. An alternative is the combination of cytokeratins CK14 and CK7, known to be negative, and CK1, known to be positive, which achieves an accuracy of 73% (33/45) in BSCC and 88% (30/34) in SCC. The two diagnostic approaches were in agreement in 66% of the cases; both methods were equally accurate in the divergent cases. Increased expression of the proliferation markers supports the concept that BSCC is a rapidly growing tumor. Results of p16 stains support an etiological link between BSCC and HPV; interestingly, HPV was present significantly more in BSCC (71% (32/45)), than in SCC (59% (20/34)) in this study (P=0.02).

p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma.

Morphologic distinction of high-grade adenoid cystic carcinoma from basaloid squamous cell carcinoma can be difficult. Equivocal diagnoses can mislead treatment. We have investigated the possibility that immunohistochemical staining for the presence of p63, a novel epithelial stem-cell regulatory protein, could be a useful means of distinguishing these two neoplasms. Archival, routinely processed slides were subjected to citrate-based antigen retrieval, exposure to anti-p63 monoclonal 4A4, and developed with a streptavidin-biotin kit and diaminobenzidine as chromogen. p63 was detected in 100% of the adenoid cystic carcinomas (n=14) and 100% of basaloid squamous cell carcinomas (n=16). Basaloid squamous cell carcinomas consistently displayed diffuse p63 positivity, with staining of nearly 100% of tumor cells. In contrast, adenoid cystic carcinoma displayed a consistently compartmentalized pattern within tumor nests. Compartmentalization was manifested in two patterns: (1) selective staining of a single peripheral layer of p63-positive cells surrounding centrally located tumor cells that were p63-negative and (2) tumor nests consisting of multiple contiguous glandular/cribriform-like units of p63-positive cells surrounding or interspersed with p63-negative cells. p63 immunostaining constitutes a specific and accurate means of distinguishing adenoid cystic carcinoma from basaloid squamous cell carcinoma. p63 positivity in adenoid cystic carcinoma appears to be homologous to that seen in the basal and/or myoepithelial compartments of salivary gland and other epithelia, and may signify a stem-cell-like role for these peripheral cells. Diffuse p63 positivity in basaloid squamous cell carcinoma suggests dysregulation of p63-positive stem cells in poorly differentiated squamous carcinoma.

Histochemical study of angiogenesis in basaloid squamous carcinoma of the esophagus.

Angiogenesis of esophageal basaloid squamous carcinoma (BSC) was studied immunohistochemically and compared with that of squamous cell carcinoma (SCC). In tissues taken from six patients with esophageal BSC and 35 with esophageal SCC, angiogenesis was evaluated by measuring microvessel density (MVD), defined as the microvessel count determined using factor VIII-related antigen immunostaining, and by measuring immunoreactivity of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (dThdPase). Three of the six patients with BSC had distant metastases. There was no difference of MVD between BSC and SCC (22.0 +/- 4.6 vs. 27.6 +/- 9.4). VEGF expression tended to be more frequently observed in BSC than in SCC (100% vs. 60.0%; p = 0.066). Strong expression of VEGF was detected in three BSC with distant metastases; however, there was no difference in the rate of strong VEGF expression between BSC and SCC. The MVD in the cases of BSC with strong VEGF expression, i.e. in the cases with distant metastases, was higher than that in the cases of BSC with weak VEGF expression (p=0.049). There was no difference in dThdPase expression of the cancer cells between BSC and SCC (50.0% vs. 54.3%), whereas the infiltrating stromal cells of all the BSC expressed dThdPase. Strong dThdPase expression in the cancer cells or in the infiltrating stromal cells was observed in two and three BSC, respectively. However, there were no differences in the rate of cancer cells or stromal cells with strong dThdPase expression between BSC and SCC. In one BSC with high MVD and distant metastases, VEGF and dThdPase were both strongly expressed. The vascularity of esophageal BSC was not different from that of SCC. VEGF may participate in angiogenesis of esophageal BSC and may influence the rate of metastasis in esophageal BSC patients. dThdPase may play a partial rule in angiogenesis and metastasis in some cases of BSC.