Mutant p53 oncogene expression in keratoacanthoma and squamous cell carcinoma

The tumour suppressor gene p53, located on the short arm of chromosome 17, encodes for a nuclear protein which regulates cell proliferation by inhibiting cells entering S-phase. p53 mutations are alleged to be the commonest genetic abnormality in human cancer. We studied mutant p53 oncoprotein expression, using PAb1801 monoclonal antibody immunohistochemistry, in 25 'ideal' keratoacanthomas and 26 well-, 19 moderately and 18 poorly differentiated squamous cell carcinomas of the skin. While there was a highly significant trend in the proportion of p53 oncoprotein-positive lesions from keratoacanthomas to poorly differentiated squamous cell carcinomas (chi 2 = 17.13, df = 1, exact P = 0.00003), p53 expression was inadequate for distinguishing keratoacanthoma from well-differentiated squamous cell carcinoma (chi 2 = 2.55, df = 1, exact P = 0.18; corresponding to a sensitivity of 0.84 and a specificity of only 0.36).     

PD-L1在皮肤鳞状细胞癌及角化棘皮瘤中的表达

目的：检测PD-L1在皮肤鳞状细胞癌（cSCC）及角化棘皮瘤（KA）中的表达,分析PD-L1与cSCC分化程度的相关性。方法：免疫组化染色检测PD-L1在cSCC及KA中表达水平。结果：共检测56例cSCC患者和32例KA患者标本，PD-L1在cSCC组和KA组中的阳性率分别为66.07%和62.50%，均显著高于正常对照组（9.38%）（Ps＜0.01）。PD-L1阳性率在cSCC与KA组的差异没有统计学意义（P＞0.05）。PD-L1的表达强度与cSCC的分化程度呈负相关（P＜0.05）。结论：PD-L1不能作为区分cSCC与KA的指标。PD-L1的表达强度与cSCC分化程度呈负相关。     

角化棘皮瘤与鳞状细胞癌增殖特性的比较研究

用PC10免疫组化染色观察了增殖细胞核抗原（PCNA）在角化棘皮瘤（KA）和鳞癌（SCC）中的表达。在KA中，PCNA阳性细胞主要分布于基底层和基底上层，而在SCC中，则广泛分布于肿瘤细胞团中。PCNA阳性指数在KA组中为22．3％～40．8％，平均32．6％，而在SCC组中则高达41．0％～80．9％，平均63．2％。两组间有显著性差异（P＜0．01），而且两组间个例PCNA阳性指数没有重叠。这种增殖特性的显著差异提示KA和SCC是两种性质不同的肿瘤。而PCNA阳性指数可能对鉴别KA和SCC有帮助。     

Cytokeratin 10 and Ki-67 nuclear marker expression in keratoacanthoma and squamous cell carcinoma

The most frequent consideration in the clinical and histologic differential diagnosis of keratoacanthoma is squamous cell carcinoma. In the present study, cytokeratin 10 expression and proliferation rate as measured by Ki-67 expression were compared between 50 clinically and histologically diagnosed keratoacanthomas and 50 squamous cell carcinomas. Tissue sections from the skin were immunohistochemically stained with anti-cytokeratin 10 and anti-Ki-67 monoclonal antibodies. The distribution of cytokeratin 10 expression and proliferative cell count were analyzed. Study results showed higher cytokeratin 10 expression in keratoacanthomas than in squamous cell carcinomas and different distribution of staining in the two entities. The analysis of cytokeratin 10 expression showed a much wider range of values and statistically higher median (p<0.001) in keratoacanthomas than in squamous cell carcinomas. Additionally, the proliferation index of keratinocytes as measured by Ki-67 expression was significantly higher in squamous cell carcinomas than in keratoacanthomas (p<0.01). These results may prove helpful in histologic differentiation of these disorders.     

DNA image cytometry of keratoacanthoma and squamous cell carcinoma

The distinction between the keratoacanthoma (KA) and the squamous cell carcinoma (SCC) can sometimes be difficult on the basis of histologic and clinical criteria. The possible diagnostic significance of DNA ploidy initiated the present study evaluating the DNA ploidy in paraffin-embedded tissue sections of 7 KA and 15 SCC, and fresh frozen tissue touch preparations of 15 of the same cases using the CAS 200 Image Analyzer. In paraffin-embedded tissue sections the main peak DNA index was based on normal epidermis, and ranged from 1.03 to 1.59 in KA and from 1.47-2.71 in SCC. The DNA Index (DI) discriminated KA from SCC in 17 of 22 cases (p less than 0.0007). The highest DNA content of single nuclei ranged from 9.0-18.0 picograms (pg) (DI 2.9-6.03) in KA and 14.8-38.6 pg (DI 4.0-11.03) in SCC. The highest DNA content discriminated KA from SCC in 16 of 22 cases (p less than 0.003). In fresh frozen tissue touch preparations from 15 of the same lesions, there was considerable overlap in DNA indices of KA (0.534-1.39) and SCC (0.464-1.41). Abnormal DNA peaks seen in histograms from three SCC in paraffin-embedded tissue sections were lost in the touch preparation histograms, probably due to inadequate sampling. Therefore, image analysis of paraffin-embedded tissue sections is better able to distinguish KA from SCC than touch preparations.     

角化棘皮瘤和皮肤鳞状细胞癌凋亡相关蛋白表达的研究

目的 探讨角化棘皮瘤(KA)与皮肤鳞状细胞癌(SCC)在细胞凋亡方面的差异.方法 消退期角化棘皮瘤(rKA)、Ⅰ级皮肤鳞状细胞癌(wdSCC)及正常皮肤,每组标本各为30例.应用免疫组化法检测上述皮损中B细胞淋巴瘤/白血病-2蛋白(Bcl-2)、天冬氨酸特异性半胱氨酸蛋白酶-3(Caspase-3)、第二线粒体衍生的半胱天冬酶激活蛋白(Smac/DIABLO)及凋亡抑制蛋白Livin表达情况.结果 Bcl-2在rKA中的表达较正常皮肤明显减少(t=3.1572,P＜ 0.05).Caspase-3在rKA中的表达较wdSCC中明显减少(t=2.1364,P＜0.05).Smac/DIABLO在正常皮肤中高表达,rKA和wdSCC中表达降低,差异有统计学意义(t=7.6141,9.5666,P值均＜0.05).Livin在正常皮肤中不表达,rKA和wdSCC中表达增高,差异有统计学意义(t=4.7913,12.7737,P值均＜0.05).Livin在rKA中的表达较wdSCC明显减少(t=7.9824,P＜0.05).结论 细胞凋亡在KA的自然消退中起到某种作用.凋亡调控蛋白Caspase-3及Livin可能有助于鉴别rKA和wdSCC.     

Proliferating cell nuclear antigen distribution in keratoacanthoma and squamous cell carcinoma

Histologic differentiation of keratoacanthoma (KA) and squamous cell carcinoma (SCC) is often difficult despite well-delineated histopathologic criteria. This has prompted a search for more objective methods to differentiate these two lesions. In the present study, we immunohistochemically examined the distribution of proliferating cell nuclear antigen (PCNA)-positive cells in 11 cases of KA, 7 cutaneous SCC, and 2 atypical squamous proliferations (for which a definitive diagnosis could not be made on routine histology) using a commercially prepared anti-PCNA monoclonal antibody. We found PCNA-positive cells predominantly in the periphery of squamous nests in KA. In contrast, SCC showed a diffuse staining pattern with PCNA-positive cells seen throughout squamous nests. Determining the pattern of PCNA-positive cells is easy, does not require cell counting, and may provide additional histochemical data facilitating the distinction between KA and SCC.     

The value of laminin-322 staining in distinguishing between keratoacanthoma, keratoacanthoma with areas of squamous cell carcinoma, and crateriform squamous cell carcinoma

IntroductionKeratoacanthoma is a fast-growing crateriform skin tumor. Approximately 25% of such tumors undergo malignant transformation and develop areas of squamous cell carcinoma (SCC). The presence of laminin-322 has been associated with progression to invasive forms of SCC. The aim of this study was to determine whether or not immunohistochemical staining for laminin-322 would be of value in distinguishing between keratoacanthomas, keratoacanthomas with areas of squamous cell carcinoma, and SCCs.Material and methodsSeventy-four lesions were selected from the pathology archives of our hospital and divided into 4 groups: 20 keratoacanthomas without SCC, 20 keratoacanthomas with areas of squamous cell carcinoma, 20 invasive SCCs (8 with crateriform morphology) unrelated to keratoacanthoma, and 14 problem lesions (keratoacanthomas with areas suggestive of SCC). All 74 lesions were stained for laminin-322.ResultsLaminin-322 staining was strongly positive both in areas of SCC in keratoacanthomas with malignant transformation and in invasive SCCs (mostly at the invasive front of the SCC). However, in benign keratoacanthomas, it was only weakly positive and furthermore it was confined to isolated cells or small groups of cells. The 14 problem lesions were reexamined after laminin-322 staining and 8 were diagnosed as keratoacanthomas with incipient SCC and 6 as keratoacanthomas without SCC.ConclusionsLaminin-322 staining is different in keratoacanthomas and SCCs and would thus be a useful test for differentiating keratoacanthomas from both invasive SCCs and keratoacanthomas with areas of squamous cell carcinoma. It would also be of value in diagnosing keratoacanthomas with areas suggestive of SCC or with incipient SCC.     

Expression of the cyclin-dependent kinase inhibitor p27 in keratoacanthoma

BACKGROUND: Keratoacanthomas are characterized by initial rapid enlargement followed by clinical regression. A series of cyclin and cyclin-dependent kinase complexes regulate cell cycle progression. p27(kip) inhibits a variety of cyclin-cyclin-dependent kinase complexes in vitro and may act to hold eukaryotic cells in a quiescent state (G0). OBJECTIVE: We examined expanding and regressing keratoacanthomas for expression of p27(kip). METHODS: An immunohistochemical method was used to visualize and count p27(kip)-labeled cells in 5 expanding and 15 regressing keratoacanthomas. RESULTS: In normal epidermis p27(kip) was found overlying the nuclei of suprabasilar keratinocytes. In expanding keratoacanthoma there was little expression of p27(kip) in nuclei of atypical keratinocytes composing the tumor (1.25 +/- 2.1 labeled cells per high-power field); in regressing keratoacanthoma the nuclei of most suprabasilar keratinocytes in atypical tumor aggregates contained p27(kip) (55.1 +/- 28.6 labeled cells per high-power field). The difference was significant at P values of less than.001. CONCLUSION: The identification of p27(kip) in regressing keratoacanthoma but not in expanding keratoacanthoma suggests that p27(kip) may be playing a role in promoting regression of keratoacanthoma and is a potential target for pharmacologic intervention.     

角化棘皮瘤和皮肤鳞状细胞癌bcl—2和Nm23癌基因蛋白表达的比较研究

目的：通过研究分析bcl-2和Nm23蛋白在角化棘皮瘤（KA）和皮肤鳞状细胞癌（SCC）中的表达和临床意义。探寻两病的鉴别标志。方法：应用免疫组化技术（SABC）对11例KA，28例SCC进行了检测。结果：bcl-2和Nm23蛋白在KA和SCC中的表达经统计学分析无显著性意义。结论：bcl-2和Nm23癌基因均参与了KA和SCC的发病过程，但都不能作为KA和SCC的鉴别标志。     

Trisomy 7 in keratoacanthoma and squamous cell carcinoma detected by fluorescence in-situ hybridization

Keratoacanthoma (KA) is generally considered to be a clinically and histologically distinct entity, but it often remains difficult to separate from well-differentiated squamous cell carcinoma (WDSCC). Recently, trisomy 7 has been identified in squamous cell carcinoma of the skin. In this study, we examined classical KA (n=6), WDSCC (n=7) and squamous cell carcinoma with KA-like features (SCC-KA) (n=8) for trisomy 7 by fluorescence in-situ hybridization (FISH) to determine if this chromosomal abnormality is unique to squamous lesions diagnosed as WDSCC, or shared by both KA and SCC. In addition, the pertinent clinical-histopathologic findings were summarized. Trisomy 7 was identified in one KA, one SCC-KA and two WDSCC. This study demonstrates that there is a chromosomal abnormality shared by KA and SCC, providing further evidence that KA is most likely a form of SCC. Further studies are required to determine if trisomy 7 in these lesions is of prognostic significance.     

Quantitation of S100 protein-positive cells in inflamed and non-inflamed keratoacanthoma and squamous cell carcinoma

Langerhans cells (LC) were identified and quantitated in non-inflamed keratoacanthoma (KA), inflamed KA, non-inflamed squamous cell carcinoma (SCC), and inflamed SCC, by their content of S100 protein. The number of LCs per high-power field was markedly increased in inflamed KA when compared to the other groups. Using similar methods on frozen sections, the expression of HLA-DR was identified on keratinocytes in KA in areas of inflammation but not in other lesions under study. We hypothesize that increased numbers of LCs in inflamed KA are part of the process which results in tumor regression.     

角化棘皮瘤与高分化鳞状细胞癌细胞凋亡及凋亡基因bcl-2和bax比较研究

目的：探讨角化棘皮瘤与皮肤高分化鳞癌在细胞凋亡方面的差异。方法：用脱氧核苷酰转移酶介导的ｄ－ＵＴＰ生物素缺口末端标记技术,原位检测了ＫＡ和ｗＳＣＣ的凋亡细胞。用免疫组化研究技术研究了皮损部位与细胞凋亡有关ｂａｘ和ｂｃｌ－２的基因产物的表达。结果：凋亡细胞在ＫＡ发生率为８０％;在ｗＳＣＣ也为８０％。     

Immunohistochemical staining for the differentiation of subungual keratoacanthoma from subungual squamous cell carcinoma

Background.  Subungual keratotic tumours are rare. The clinical and histological distinctions between subungual keratoacanthomas (SUKAs) and subungual squamous cell carcinomas (SCCs) are important, but often difficult. Adequate methods of differentiation between the two are required, both for the purpose of management and for assessment of prognosis.
Aim.  To establish the value of immunohistochemical staining patterns of proliferating cells to distinguish between SUKAs and subungual SCCs.
Methods.  In total, 20 keratotic tumours from 20 patients were examined with immunohistochemical staining techniques using bcl- 2, Ki67 and p53.
Results.  Of 20 patients, 4 had SUKAs, 5 had cutaneous KAs, 6 had subungual SCCs and 5 had cutaneous SCCs. Our results showed that a high index of staining of p53 favours the diagnosis of subungual SCC over SUKA.
Conclusion.  SUKAs do not express Ki67 strongly whereas some subungual SCCs do. Thus we conclude that immunohistochemistry for p53 and Ki67 may help distinguish between a subungual SCC and a SUKA.     

Utility of peanut agglutinin (PNA) in the diagnosis of squamous cell carcinoma and keratoacanthoma

Lectins are glycoproteins that bind to specific carbohydrate groups on cell surfaces. Peanut lectin (PNA) binds to carbohydrates on the membranes of normal keratinocytes. Recently, some authors have proposed that PNA may be a useful marker to help differentiate keratoacanthomas from well-differentiated squamous cell carcinomas of the skin. We studied a total of 34 skin biopsy specimens, including 11 keratoacanthomas, 15 well-differentiated squamous cell carcinomas, and 8 poorly differentiated squamous cell carcinomas, using peanut lectin with the avidin-biotin complex (ABC) peroxidase technique. All keratoacanthomas demonstrated uniform positive membrane staining of keratinocytes, which was identical to PNA staining in normal skin. Keratinocytes in 80% of the well-differentiated squamous cell carcinomas and keratinocytes in all the poorly differentiated squamous cell carcinomas did not stain. With prior digestion by neuraminidase, however, positive membrane staining for PNA was demonstrated in the squamous cells of all well-differentiated squamous cell carcinomas and all but one case of the poorly differentiated squamous cell carcinomas. Our results support the efficacy of PNA in most cases as a marker to aid in the often difficult histologic differentiation of keratoacanthoma from well-differentiated squamous cell carcinoma. Our findings also support those of previous authors who suggested that the negative PNA stain of malignant squamous cells is not the result of a lack of PNA receptors, but is due instead to a masking of receptor sites by terminal sialic acid residues.     

Eruptive keratoacanthoma and squamous cell carcinoma complicating imiquimod therapy: response to oral acitretin

An 87-year-old woman with eruptive keratoacanthomas complicating recent imiquimod therapy is presented. Lesions developed both at and distal to the treatment site. She responded well to 8 weeks of oral acitretin with resolution of most lesions and no recurrence at 6 months post treatment. A remaining lesion was excised and found to be a well-differentiated squamous cell carcinoma. Keratoacanthoma and squamous cell carcinoma should be considered in any patient developing rapidly growing keratotic nodules in association with recent imiquimod therapy. The aetiology and treatment of eruptive keratoacanthomas is briefly discussed.