The Immune Response of Cutaneous Basosquamous- and Squamous-Cell Carcinoma Associated with Sun Exposure.

In recent years, there has been an observed increase in the frequency of cutaneous carcinoma, which correlates with sun exposure. This study aims to explore the variances of tumor characteristics and immune response markers among patients diagnosed with cutaneous squamous-cell carcinoma (SCC) and basosquamous-cell carcinoma (BSC) with varying levels of sun exposure. The objective is to elucidate the potential influence of sun exposure on tumor progression and immune response in these types of carcinomas. We conducted a retrospective observational study that included 132 patients diagnosed with SCC and BSC. Participants were separated into high- and low-sun exposure groups. Tumor characteristics and immune response markers, including lymphocyte percentage (LY%), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR), were assessed using the Mann-Whitney U test. Our findings revealed the interplay between sun exposure, inflammation, aging, and immune response. In 80% of cases, it was found that individuals had high sun exposure throughout their lifetime. Patients in the high sun exposure category had a significantly higher LY% than those with low sun exposure (24.22 ± 7.64 vs. 20.71 ± 8.10, p = 0.041). Also, the NLR was lower in patients with high sun exposure (3.08 ± 1.47 vs. 3.94 ± 2.43, p = 0.023). Regarding inflammatory markers, the erythrocyte sedimentation rate (ESR), LY%, NLR, and LMR showed significant differences between the two groups. Patients who were diagnosed with SCC had higher ESR values (p = 0.041), higher LY% (p = 0.037), higher NLR (p = 0.041), and lower LMR (p = 0.025). This study provides evidence supporting distinct tumor characteristics and immune response patterns in patients diagnosed with SCC and BSC with a high sun exposure history. These findings imply that sun exposure may contribute to tumor progression and influence the immune response in individuals with SCC and BSC.

Utility of Ber-EP4 and MOC-31 in Basaloid Skin Tumor Detection.

Ber-EP4 has been the traditional immunostain used for the detection of basaloid skin tumors. Recently, MOC-31 has shown be superior to Ber-EP4 in the detection of basosquamous basal cell carcinoma (BCC) and many centers are now using both Ber-EP4 and MOC-31 antibodies together to detect these lesions. The objective of this study was to compare the utility of using both Ber-EP4 and MOC-31 immunostains in the detection of basaloid skin tumors and to better characterize the previously unknown staining properties of MOC-31 in cutaneous lesions. To do this, 76 basaloid skin tumors stained with both Ber-EP4 and MOC-31 were obtained. Diagnoses included basosquamous BCC, Merkel cell carcinoma, adenoid cystic carcinoma, microcystic adnexal carcinoma, sebaceous carcinoma, trichoepithelioma, trichoblastoma, sebaceous adenoma, sebaceoma, and follicular induction overlying dermatofibroma. The distribution and intensity of Ber-EP4 and MOC-31 staining in these lesions was scored. These scores were analyzed using a truth table, χ test, and Pearson correlation tests. The overall mean and SD of the scores were also obtained. Overall, we found Ber-EP4 and MOC-31 to be statistically equivalent immunostains for the diagnosis of basaloid skin tumors. We recommend the use of only one of these antibodies and favor MOC-31 for the detection of basaloid skin tumors. We also describe MOC-31 staining properties in different cutaneous lesions.

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.

Histological diversity in basaloid squamous cell carcinoma of the esophagus.

Basaloid squamous cell carcinoma of the esophagus (BSCCE) is a distinct variant of esophageal cancer. This study investigated histopathological variations of BSCCE. Thirty-eight surgical and two endoscopically resected specimens of BSCCE were examined. Histological features were classified into five components: solid nest (SN), microcyst and/or trabecular nest (MT), ductal differentiation (DD), cribriform pattern (CP), and an invasive squamous cell carcinoma (SCC) component. The immunohistochemical phenotypes of each component were examined using antibodies against cytokeratin (CK) 7, CK14, and alpha smooth muscle actin (SMA). SN, MT, DD, CP, and SCC were present in 95.0, 97.5, 27.5, 32.5, and 82.5% of the cases, respectively, and combinations of SN & MT, SN & DD, SN, MT & DD, SN, MT & CP, and SN, MT, DD & CP were found in 50.0, 2.5, 10.0, 17.5, and 15.0%, respectively. All the intraepithelial lesions observed in 18 (45.0%) cases were SCC. Immunoreactivity for CK7, CK14, and SMA was seen in 10.5, 86.8, and 18.4% of SN; 30.8, 97.4, and 38.5% of MT; 54.5, 100.0, and 54.5% of DD; 7.7, 76.9, and 23.1% of CP; and 6.1, 97.0, and 0.0% of SCC, respectively. CK14 immunoreactivity was seen in the periphery of most of the SN component. CK7, CK14, and SMA immunoreactivity was seen in the inner layer, all layers, and the outer layer of DD, respectively. MT and CP showed partial peripheral positivity for CK14 and SMA in microcystic, trabecular, and cribriform-like pseudoglandular structures. BSCCE demonstrates various histopathological and immunohistochemical features including a ductal and cribriform growth pattern.

Expression of PCNA and bcl-2 in basaloid squamous cell carcinoma of the larynx: a controlled study.

We investigated the difference in the biologic nature of typical squamous cell carcinoma (SCC) and basaloid SCC (BSCC) of the larynx by studying proliferation and antiapoptotic markers. We performed an immunohistochemical analysis of the expression of proliferating cell nuclear antigen (PCNA) and bcl-2 protein in 15 patients with laryngeal BSCC and 15 stage- and site-matched controls with typical laryngeal SCC. We found no significant difference between the two groups in the PCNA index or the frequency of bcl-2 overexpression, nor did we find any significant difference in survival. Our findings indicate that the biologic nature of typical laryngeal SCC and laryngeal BSCC is similar. In addition, our follow-up data suggest that the clinical course of laryngeal BSCC is no worse than that of typical laryngeal SCC.

The pathomorphology of a human xenotransplanted basaloid squamous cell carcinoma.

To elucidate some factors related to the malignant phenotype of an oral tumor with mixed cell population the question has been raised whether the biological behavior of the basaloid or the squamous cells show any difference in an immunosuppressed host organism. Basaloid squamous cell carcinoma (BSCC) surgically removed from sublingual location was xenotransplanted either subcutaneously or in the oral submucosa and the histology, ultrastructures, LDH isoenzyme pattern were investigated. The epithelial origin of the established tumor line (HTB-1) could be recognized according to the characteristic epithelial ultrastructures, while the type of the LDH isoenzymes proved its human origin. The squamous cell population dominating the parent surgical specimen of BSCC regressed during xenotransplantation in the subcutan location, on the contrary the basaloid cells grew and maintained the tumor. Interestingly the basaloid cells transplanted from the subcutis to the oral submucosa generated a squamous cell population with an infiltrative growth pattern. The xenografted BSCC offer a promising model to investigate the contribution of each cell populations in the malignant phenotype. The presented data indicate that the basaloid cells are responsible for maintaining the tumor cell population, but certain malignant features (i.e. infiltrative growth) is associated to the squamous cells which are generated from the basaloid cells only under specific circumstances. Thus this particular model system showed that different malignant features could be associated to the basaloid and to the squamous cell component.

[Basal cell and basosquamous carcinomas of the external ear. Immunohistochemical study]. / Carcinomi basocellulari e basosquamosi dell'orecchio esterno. Tipizzazione immunocitochimica.

Malignant neoplasms of the external ear are difficult diseases of the cervical-facial area to study clinically and therapeutically. The most frequent malignant histological patterns are spinocellular and basocellular carcinomas. Melanomas, basosquamous or "metatypical" carcinomas are less frequent. The latter have a transition histological pattern halfway between a basocellular and spinocellular carcinoma. In our experience, some external ear neoplasms, diagnosed as basocellular, were clinically more invasive (aggressive). Therefore we studied the immunohistochemistry of operative specimens with monoclonal antibodies (MoAb) with the purpose of revaluating the diagnosis after follow-up, and of detecting unrecognized basosquamous carcinomas. We studied 4 patients (2 male and 2 female) aged between 58 and 78, examined in the period 1990-92 an a diagnosed as having an external ear basocellular carcinoma. The immunohistochemical study was carried out using anti-CEA (carcinoembryonal antigen) monoclonal antibodies, high molecular weight acid anticytokeratins (anti-AE3) and low molecular weight basic anticytokeratins (anti-AE1). Appendage origin of the neoplasms was excluded after carrying out MoAb anti-CEA tests, negative in all patients. Epithelial origin of the neoplasms were confirmed after carrying out MoAb anti-AE3 tests, positive in all patients. After carrying out MoAb anti-AE1 tests, positive in 3 patients out of 4, we reviewed the classification of 2 basocellular carcinomas out of 4. These tumors evidenced an atypical dyskeratosis and a positivity for intracellular keratinization. These aspects were not evidenced in the previous histological examinations using routine stains and could be an index of unfavourable clinical evolution of these two cases from a basocellular carcinoma toward a more aggressive basosquamous carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Basaloid-squamous carcinoma of the upper aerodigestive tract and so-called adenoid cystic carcinoma of the oesophagus: the same tumour type?

Basaloid-squamous carcinoma of the larynx, pharynx and base of tongue and the so-called adenoid cystic carcinoma of the oesophagus are rare but distinctive tumours associated with a grave prognosis. They occur most commonly in elderly males and present at an advanced stage. Our study of four such laryngeal tumours and five such oesophageal tumours shows that they are histologically and immunohistochemically identical, providing support for the idea that they are the same tumour type. They show a biphasic pattern in which basaloid tumour is intimately associated with a neoplastic squamous component which can be invasive or in situ. The basaloid component is in the form of invasive lobules with frequent comedo-necrosis and hyalinization. The constituent cells possess pale pleomorphic nuclei with frequent mitoses. Immunoreactivity for cytokeratin in the basaloid component is remarkable for its absence or weak and focal nature. Review of the literature shows that only a few cases of 'adenoid cystic carcinoma' of the oesophagus are bona fide examples of adenoid cystic carcinoma as it occurs in the salivary glands, while the others are identical to basaloid-squamous carcinoma of the upper aerodigestive tract. Their distinction is important because genuine adenoid cystic carcinoma is much less aggressive than basaloid-squamous carcinoma.

Discontinuity of the basement membrane in fibrosing basocellular carcinomas and basosquamous carcinomas of the skin: an immunohistochemical study with human laminin and type IV collagen antibodies.

Thirteen basocellular carcinomas (BCC) of different histologic types and 5 basosquamous carcinomas (BSC) of the skin were stained for laminin and type IV collagen with rabbit antibodies against the human basement membrane (BM) proteins, using an immunoperoxidase technique. The BM around the tumor aggregates contained both laminin and type IV collagen, and was continuous and distinct in all the nonfibrosing BCCs but indistinct or interrupted in the fibrosing BCCs and BSCs. The BM was not influenced by the focal adnexal differentiation of the BCC cells. The disintegrity of the BM in the fibrosing BCCs and BSCs may reflect some kind of disturbance in the interaction between the neoplastic epithelium and the connective tissue stroma, and be connected with the more aggressive nature of these tumors compared with ordinary BCCs. Thus local aggressive behavior seems to be accompanied by defects in the BM.

Identification of a colon-specific antigen (CSA) in normal and neoplastic tissues.

An antigen has been isolated from a human signet-ring cell carcinoma serially growing in hamsters, GW-39, by saline, PCA, or phenol extraction, and has been found immunologically identical to a similarly extracted substance in normal human or hamster colon. No other hamster or human tissues or cells were found to contain this antigen, for which reason we have termed it colon-specific antigen, or CSA. CSA has been found to be distinct from the major blood group-specific antigens and from othercolon tumor-associated antigens, such as CEA, CCA-II, and CCA-III. It thus seems that a colon organ-specific antigen can be synthesized by this particular human tumor system. Hamsters immunized with CSA could reject cheek pouch grafts of GW-39 tumors, and tumor rejection by these animals correlated with their anti-CSA antibody titers. Preliminary characterization of CSA suggested that it is a glycoprotein on the cell surface having a molecular size of 30,000 to 50,000 daltons. It is proposed that CSA may play a role in the diagnosis of mucin-producing adenocarcinoma of the colon and in ulcerative colitis.

Antigenic constituents in pregnancy plasma which are undetectable in normal non-pregnant female or male plasma.

PIP: To detect antigens in the plasma of pregnant women that were not found in nonpregnant untreated normal women or males, highly sensitive immunodiffusion techniques with hyperimmune rabbit antiserum were used. The number of pregnancy-associated plasma constituents increased as pregnancy progressed in the 165 patients studied, with all 4 constituents usually seen in the third trimester. The 60 males and 111 nonpregnant women studied did not show any of these antigens. There were significant differences between second and third trimester reactions. (p less than .001). None of the antigens represented human chorionic gonadotropin, human placental lactogen, oxytocin, C-reactive protein, oxytocinase, alkaline phosphatase, or esterase. One of these constituents is present during combined estrogen-progesterone therapy.^ieng