Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens.

Using an indirect immunoperoxidase technique, 20 nevocellular nevi, 5 dysplastic nevi, 14 primary cutaneous melanomas, and 24 metastatic melanomas were tested with a panel of monoclonal antibodies to monomorphic determinants of Class I (HLA-A,B,C) and Class II (la-like) major histocompatibility complex antigens. Class I HLA and beta 2-microglobulins were not detected on the majority of nevus cells but were expressed by 3 of 5 dysplastic nevi, by the majority of tumor cells in 12 of 14 primary cutaneous melanomas, and in 13 of 24 metastases. The different expression of Class I HLA and beta 2-microglobulins in primary and metastatic lesions suggests that loss of these antigens may be associated with progression of malignancy. Class II HLA were not detected in common nevi but were locally present in 1 of 5 dysplastic nevi, 7 of 14 cases of primary cutaneous melanoma, and all 24 cases of metastatic lesions tested. These findings suggest that increase in Class II HLA expression may be associated with progression of malignancy. The staining patterns obtained with monoclonal antibodies to distinct determinants of Class I HLA and Class II HLA were superimposable within each type of antigen. Therefore, the discrepancies in the literature about the expression of histocompatibility antigens by lesions of melanocytic origin are not likely to reflect the different specificity of the antibodies used by the various investigators.

Impact of global genome repair versus transcription-coupled repair on ultraviolet carcinogenesis in hairless mice.

The nucleotide excision repair (NER) system is comprised of two subpathways, i.e., transcription-coupled repair (TCR) and global genome repair (GGR). To establish the relative importance of TCR and GGR for UV effects on the skin, we have used hairless knockout mouse strain lacking either TCR (CSB -/-) or GGR (XPC -/-). In single exposure experiments, we found that CSB -/- mice have a 7-16 times higher susceptibility to sunburn than XPC -/- mice and than heterozygous (+/-) and wild-type (+/+) controls. Exposure to 80 J/m2 UV radiation (i.e., suberythemogenic in CSB -/-) on 10 consecutive days gives rise to epidermal hyperplasia in CSB -/- and XPC -/-, whereas repair-proficient controls do not show epidermal hyperplasia from these exposures. In addition, CSB -/- mice develop marked parakeratosis, whereas XPC -/- mice and controls do not. Under continued exposure to this daily dose, squamous cell carcinomas appear in CSB -/-, XPC -/-, and in the control groups, whereas only in the CSB -/- animals is a fairly high number of benign papillomas also found. The median latency time of squamous cell carcinomas (diameters > or = 1 mm) is 84 days for the XPC -/- mice, 115 days for the CSB -/- mice, and 234-238 days for the heterozygous and wild-type control groups. These results indicate that GGR is more important than TCR in protection against UV-induced carcinomas of the skin but not against other UV effects such as sunburn, epidermal thickening, scaling of the stratum corneum, and development of papillomas. These results also indicate that GGR capacity may serve as a better predictor for skin cancer susceptibility than sensitivity to sunburn. The relative cancer susceptibilities of GGR- and TCR-deficient skin could well depend on the balance between an increased mutation rate and the presence (in CSB -/-) or lack (in XPC -/-) of a compensatory apoptotic response.

Prognostic factors in primary cutaneous large B-cell lymphomas: a European multicenter study.

PURPOSE: Most primary cutaneous B-cell lymphomas have an excellent prognosis. However, primary cutaneous large B-cell lymphomas (PCLBCLs) of the leg have been recognized as a distinct entity with a poorer prognosis in the European Organization for Research and Treatment of Cancer (EORTC) classification. This distinction on the basis of site has been debated. Our aim was to identify independent prognostic factors in a large European multicenter series of PCLBCL. PATIENTS AND METHODS: The clinical and histologic data of 145 patients with PCLBCL were evaluated. According to the EORTC classification, 48 patients had a PCLBCL of the leg and 97 had a primary cutaneous follicle center-cell lymphoma (PCFCCL). Data from both groups were compared. Univariate and multivariate analyses of specific survival were performed using a Cox proportional hazards model. RESULTS: Compared with PCFCCL, PCLBCL-leg were characterized by an older age of onset, a more recent history of skin lesions, a more frequent predominance of tumor cells with round nuclei and positive bcl-2 staining, and a poorer 5-year disease-specific survival rate (52% v 94%; P <.0001). Univariate survival analysis in the entire study group showed that older age, a more recent onset of skin lesions, the location on the leg, multiple skin lesions, and the round-cell morphology were significantly related to death. In multivariate analysis, the round-cell morphology (P <.0001), the location on the leg (P =.002), and multiple skin lesions (P =.01) remained independent prognostic factors. The round-cell morphology was an adverse prognostic factor both in PCLBCL-leg and in PCFCCL, whereas multiple skin lesions were associated with a poor prognosis only in patients with PCLBCL-leg. CONCLUSION: With site, morphology, and number of tumors taken into account, guidelines for the management of PCLBCL are presented.

Treatment of multifocal primary cutaneous B-cell lymphoma: a clinical follow-up study of 29 patients.

PURPOSE: Although patients with primary cutaneous B-cell lymphoma (CBCL) and localized skin lesions are generally treated with radiotherapy and have an excellent prognosis, the clinical behavior and optimal treatment of CBCL presenting with multifocal skin lesions are less well defined. In this study, we evaluated the clinical behavior of and results of treatment for multifocal CBCL in 29 patients, and we formulated therapeutic guidelines. PATIENTS AND METHODS: The study group included 16 patients with primary cutaneous follicular center-cell lymphoma (PCFCCL), eight with primary cutaneous immunocytoma (PCI), and five with primary cutaneous large B-cell lymphoma presenting on the legs (PCLBCL of the leg). RESULTS: Only one of the 24 patients with multifocal PCFCCL or PCI developed extracutaneous disease, and no patient died from lymphoma (median follow-up, 54 months). In patients with PCFCCL, treatment with either multiagent chemotherapy (nine patients) or radiotherapy directed toward all skin lesions (five patients) proved equally effective in terms of complete remission, relapse, and survival. In contrast, all five patients with PCLBCL of the leg developed extracutaneous disease, and four of the five died from systemic lymphoma, 8 to 36 months (median, 21 months) after diagnosis. CONCLUSION: The results of these preliminary studies suggest that patients with PCFCCL or PCI presenting with multifocal skin lesions have the same excellent prognosis that patients with localized PCFCCL or PCI have and that radiotherapy directed toward all skin lesions is as effective as multiagent chemotherapy. Patients with PCLBCL of the leg have a more unfavorable prognosis, particularly patients presenting with multifocal skin lesions. This last group should always be treated with multiagent chemotherapy.

DNA-cytophotometry of lymph node imprints from patients with mycosis fungoides.

To obtain objective criteria for early diagnosis of lymph node involvement in patients with mycosis fundoides, Feulgen DNA-cytophotometry was carried out in lymph node imprints from patients with mycosis fungoides. The lymph nodes of 3 patients with lymph nodes, showing partial or total replacement by atypical lymphoreticular tissue histologically, showed a polyploid and aneuploid DNA distribution. Eleven out of 22 patients with dermatopathic lymphadenopathy both with or without early involvement histologically had an abnormal DNA histogram with hypertetraploid DNA values. Four of these 11 died, 5 had a partial remission in response to therapy and 2 had sustained remission during the follow-up period of 5 yr. The other 11 patients had a normal DNA distribution. Of these 11, one died and 10 achieved sustained remission after therapy. There is a good correlation between the DNA-cytophotometric results and histology of the lymph nodes. On the basis of these results DNA-cytophotometry may be considered an additional and objective aid in the diagnosis of lymph node involvement in mycosis fungoides.

Diagnostic criteria in Sézary's syndrome: a multiparameter study of peripheral blood lymphocytes in 32 patients with erythroderma.

In order to define additional diagnostic criteria for the early diagnosis of Sézary's syndrome (SS), peripheral blood lymphocytes of 32 patients with erythroderma, including 8 patients with SS, 4 patients with erythrodermic mycosis fungoides, 14 patients with an erythroderma on the basis of atopic or chronic dermatitis, and 6 patients with erythrodermic psoriasis, were investigated by computer-assisted morphometry. The degree of nuclear indentation, expressed as the nuclear contour index (NCI), was measured on electron micrographs. The mean NCI and the percentages of cerebriform mononuclear cells (CMC), defined by a NCI greater than or equal to 6.5, were calculated. In addition, the percentages of lymphocytes, T and B cells, and the distribution of T-cell sub-populations as defined by Fc-receptors (T mu, T gamma) and monoclonal antibodies (OKT3, OKT4, OKT8, HLA-DR) were determined. Statistical analysis showed as most discriminating parameters for the differentiation between SS and benign forms of erythroderma: high percentages of lymphocytes (50% or more), an expanded OKT3+, OKT4+ population with an OKT4/OKT8 ratio greater than 10, a mean NCI value greater than or equal to 5.5, the presence of more than 20% CMC, as well as the presence of cells with a NCI greater than or equal to 11.5. The total leukocyte and lymphocyte counts, as well as the percentages of B, T, T mu, and T gamma cells had limited value for the early diagnosis of SS.

Influence of ultraviolet B exposure on immune responses following hepatitis B vaccination in human volunteers.

Exposure to ultraviolet radiation can modulate immune responses in animal and humans. Remarkably, the ultraviolet-induced immunosuppression is not restricted to the exposed skin but is also found at other body sites, i.e., systemic immunosuppression. Effects of ultraviolet radiation on infections cannot be determined by experimentation on humans, but the effects of ultraviolet on vaccination may serve as a model. Moreover, it is important in its own right to assess whether ultraviolet radiation affects vaccination responses. In this study the effect of ultraviolet B exposure on the development of immune responses after hepatitis B vaccination in human volunteers was investigated. To this end, 191 human volunteers were vaccinated against hepatitis B with the Engerix-B vaccine. Ninety-seven of them were prior to the first vaccination exposed to ultraviolet B on 5 consecutive days with one personal minimal erythema dose per day. At several time-points before and after the ultraviolet B exposure regimen and the vaccination, blood samples were taken. Parameters for specific as well as nonspecific cellular and humoral immunity were analyzed. It was demonstrated that ultraviolet B exposure prior to hepatitis B vaccination did not alter the cellular (lymphocyte stimulation test) nor the humoral (antibody titers) immune response against hepatitis B surface antigen significantly. In contrast, contact hypersensitivity to diphenylcyclopropenone was significantly suppressed after ultraviolet B exposure, as was natural killer cell activity. These latter results confirm earlier findings and demonstrate immunosuppressive effectiveness of the ultraviolet regimen. In summary, although natural killer cell activity and contact hypersensitivity responses were suppressed, the ultraviolet B radiation protocol did not alter the humoral nor the cellular immune responses against hepatitis B surface antigen after vaccination.

Ultraviolet radiation--induced impairment of the early initiating and the late effector phases of contact hypersensitivity to picrylchloride: regulation by different mechanisms.

Two types of antigen-specific T cells are needed for the elicitation of contact hypersensitivity reactions. They act in an obligate sequence to mediate the early initiating and late effector phases of contact hypersensitivity, which are accompanied by skin-swelling responses at 2 and 24 h after challenge, respectively. The magnitude of the late ear swelling depends on that of the early swelling. We studied the influence of ultraviolet radiation on both phases of contact hypersensitivity to picrylchloride. Mice were exposed to subedemal doses of ultraviolet radiation on the shaved backs for four consecutive days. Four days later mice were sensitized on non-irradiated skin. Four days after sensitization mice were challenged on the ears, and swelling was measured 2, 4, and 24 h after challenge. The early and late phases of contact hypersensitivity were largely suppressed in ultraviolet-irradiated, actively sensitized mice. Transfer of immune lymphoid cells from donor mice that were sensitized 4 d earlier induced early and late components of contact hypersensitivity in naive recipients after challenge. Transfer of immune lymphoid cells from donors that were sensitized 1 d earlier only induced the early component of contact hypersensitivity. Ultraviolet irradiation of donor mice significantly reduced the capacity of the immune lymphoid cells to induce contact hypersensitivity. We show that lymphoid cells responsible for the early and late components of contact hypersensitivity are both affected.

T-cell receptor V beta-family usage in primary cutaneous and primary nodal T-cell non-Hodgkin's lymphomas.

To evaluate whether the expression of T-cell receptor (TCR) V beta families in eight cases of malignant T-cell lymphomas took place in a preferential manner, we analyzed four cases of mycosis fungoides (MF), the most common form of primary cutaneous T-cell non-Hodgkin's lymphomas (NHL), and four cases of primary nodal T-cell NHL. The usage of V beta families in T-cell populations was investigated on mRNA that was transcribed to cDNA using a C beta primer and reverse transcriptase. Subsequently, the specific usage of the families was analyzed by polymerase chain reaction (PCR) using combinations of the selected C beta-oligonucleotide primer and one of the family-specific V beta primers. Peripheral blood lymphocytes from four healthy volunteers and 1 "reactive" lymph node served as a control and expressed all 20 V beta families tested for. In T-cell lines, with restricted V beta expression, and in three patients with advanced MF, only one or two V beta families were expressed at the mRNA level. In an early MF lesion this monoclonal expression was absent: several V beta families were expressed with a weak intensity. This may indicate either a polyclonal origin of MF, or that too few monoclonal neoplastic cells were present in the tissue specimen. In the four nodal T-cell NHL, only one family could be clearly distinguished, whereas some of the other V beta families showed only a weak expression. These latter families represent the reactive T-cell component in the nodal T-cell NHL. Both in nodal T-cell NHL and in MF there was no preferential expression of a particular V beta family. There was a good correlation between PCR data and the expression of V beta-family protein products observed by immunohistochemistry on tissue sections of the T-cell lymphomas. All T-cell lines, three cases of MF, and three cases of nodal T-cell NHL showed a rearrangement of the TCR beta chain on DNA level.

Cells with UV-specific DNA damage are present in murine lymph nodes after in vivo UV irradiation.

Ultraviolet radiation is absorbed in the skin, especially in the epidermis. After ultraviolet irradiation the number of major histocompatibility complex class II+, adenosine triphosphatase+ Langerhans cells and Thy-1+ dendritic epidermal cells in the epidermis decreases. Whether this decrease is due to migration of these cells or to loss of membrane markers is not clear. To address this question we have used the monoclonal antibody H3 directed against cyclobutyl thymine dimers-a form of DNA damage that is specifically induced by ultraviolet radiation-to investigate whether H3+ cells are present in the draining lymph nodes of the skin after ultraviolet irradiation of hairless, inbred mice (HRA/Skh). After a single dose of ultraviolet radiation (Westinghouse FS40, 1.5 kJ/m2), H3+ cells were present in the paracortex of the draining lymph nodes. No positive cells were found in the blood of irradiated mice. These results suggest that the H3+ cells in the lymph nodes originate from the skin. The number of H3+ cells in the draining lymph nodes increased the first 24 h after irradiation and then stabilized. Immunohistochemical double staining revealed that all H3+ cells were major histocompatibility complex II+, and that only a fraction of the cells were NLDC-145 positive. No V gamma 3 T-cell receptor bearing cells could be found in the lymph nodes after UV irradiation of the skin.

CD11b+ cells and ultraviolet-B-resistant CD1a+ cells in skin of patients with polymorphous light eruption.

After ultraviolet exposure Langerhans cells (epidermal CD1a+ cells) disappear from the healthy skin, and CD11b+ macrophage-like cells, which are reported to produce interleukin-10, appear in a matter of days. These phenomena are related to the ultraviolet-induced local suppression of contact hypersensitivity reactions. A defect in this suppression might allow inadvertent immune reactions to develop after ultraviolet (over)exposure; i.e., it could cause ultraviolet-B-induced polymorphous light eruption. In order to test this we first exposed buttock skin of eight healthy volunteers to six minimal erythema doses from Philips TL12 lamps, and indeed observed a dramatic disappearance of CD1a+ cells 48 and 72 h later, at which time the number of CD11b+ cells increased in the dermis, and some occurred in the epidermis. The epidermis thickened and showed large defects, filled by CD11b+ cells, just below the stratum corneum. In 10 patients with polymorphous light eruption (five with a normal minimal erythema dose and five with a low minimal erythema dose) CD1a+ cells were present in the epidermis as well as in the dermis before exposure. Strikingly, these cells were still present in considerable number at 48 and 72 h after exposure to six minimal erythema doses. CD11b+ cells already present in the dermis before ultraviolet exposure, increased after ultraviolet exposure, and subsequently also invaded the epidermis. Despite the six minimal erythema doses, there were no apparent defects in the epidermis of the polymorphous light eruption patients. This deviant early response to ultraviolet radiation is likely to be of direct relevance to the polymorphous light eruption and is perhaps useful as a diagnostic criterion.

Regulatory activity of neoplastic T cells in Sezary syndrome on in vitro immunoglobulin production.

Functional activities and surface markers of the neoplastic T cells of three patients with Sézary syndrome were studied and compared with the functional activities of OKT4+ and OKT8+ T-cell subsets from healthy donors. The neoplastic T cells of the patients had the following marker phenotype: OKT1+3+4+6-8-11+17+I1-M1-3A1-. In contrast to healthy donor OKT4+ T cells, none of the neoplastic T cells had significant helper activity on pokeweed-mitogen-driven Ig synthesis. In one patient the neoplastic T cells suppressed pokeweed-mitogen-driven Ig synthesis. The suppression by the patient cells did not require the presence of radiosensitive OKT4+ suppressor-inducer cells in the culture. It is concluded that OKT4+8-3A1- neoplastic T cells from Sézary-syndrome patients lacking helper activity are more common than previously thought and that in some cases the OKT4+8-3A1- Sézary cells can mediate suppressor activity.

Treatment of mycosis fungoides: total-skin electron-beam irradiation vs topical mechlorethamine therapy.

Of 42 patients who had mycosis fungoides (MF) confined to the skin with or without dermatopathic lymphadenopathy, 21 were treated with topically applied mechlorethamine hydrochloride and 21 with total-skin electron-beam irradiation. The results of both therapeutic modalities are compared. We conclude that, in the early stage of the disease, both forms of treatment are equally effective. In the later stages of MF, in the absence of lymph node or other systemic involvement, electron-beam irradiation seems to be superior in inducing an initial complete remission. However, because of the large number of patients who have a relapse after this therapy, it should be followed by topical mechlorethamine therapy.

Familial elastosis perforans serpiginosa.

BACKGROUND: Elastosis perforans serpiginosa (EPS) is an uncommon skin disease characterized by transepidermal elimination of abnormal elastic fibers. The disease is frequently associated with congenital connective tissue disorders or Down's syndrome. The pathogenesis of EPS is still unclear. There are a few reports in the literature about a familial occurrence of EPS in which different modes of inheritance are suggested. To support the hypothesis of a congenital origin of the disease, we have studied another family with EPS. OBSERVATIONS: In this study, we describe a family in which two sisters and a brother were affected by EPS. The father and three paternal uncles were most probably affected by the same disease. There were no signs of other congenital connective tissue disease in the family members. CONCLUSION: An autosomal dominant mode of inheritance with variable expression of EPS is suggested.

Skin lesions due to exposure to methyl bromide.

Six patients were occupationally exposed to high concentrations of methyl bromide during a fumigation procedure using adequate airway protection. Within a few hours all patients developed skin lesions, consisting of sharply demarcated erythema with multiple vesicles and large bullae. There was a striking predisposition for parts of the skin that were relatively moist or subject to mechanical pressure, such as axillae, groin, and abdomen. Microscopically, early skin lesions revealed necrosis of keratinocytes, severe edema of the upper dermis, subepidermal blistering, and diffuse infiltration of neutrophils and, to a lesser degree, eosinophils. Two patients developed an urticarial rash approximately one week after the exposure. On histologic examination, these late lesions showed combined features of a spongiotic dermatitis and urticaria. No immunopathologic manifestations were observed. In all patients, the skin returned to normal after four weeks, except for some residual hyperpigmentation. Plasma bromide levels after exposure strongly suggested percutaneous absorption of methyl bromide.

Primary cutaneous large B-cell lymphomas of the legs. A distinct type of cutaneous B-cell lymphoma with an intermediate prognosis. Dutch Cutaneous Lymphoma Working Group.

BACKGROUND AND DESIGN: Primary cutaneous follicular center cell lymphomas represent a distinct type of cutaneous B-cell lymphoma, clinically characterized by localized skin lesions on the head or trunk and an excellent prognosis. Histologically similar lymphomas may occur on the legs. The clinical behavior of this group is still undefined, and controversy exists whether these lymphomas should be classified as follicular center cell lymphoma or B-immunoblastic lymphoma. We reviewed the clinical, histologic, and follow-up data of 18 patients with primary cutaneous large B-cell lymphoma of the legs. RESULTS: Primary cutaneous large B-cell lymphoma of the legs generally occurred in elderly patients (median age at diagnosis, 76 years), in particular women (male-female ratio, 7:2), and preferentially affected the lower legs (14 of 18 patients). Radiotherapy and/or systemic polychemotherapy resulted in complete remissions in 16 of 17 patients. Follow-up data demonstrated estimated 2- and 5-year survival rates of 77% and 58%, respectively. Histologic evaluation showed diffuse dermal infiltrates with variable proportions of centroblasts (large noncleaved cells), large centrocytes (large cleaved cells), and B immunoblasts. Seventeen of 18 patients were diagnosed as having primary cutaneous follicular center cell lymphoma; only 1 patient, whose histologic examination showed more than 30% immunoblasts, was diagnosed as having B-immunoblastic lymphoma. CONCLUSIONS: Primary cutaneous large B-cell lymphoma of the legs is a distinct clinicopathologic entity that mainly affects elderly patients and has an intermediate prognosis. Although most cases have a follicular center cell origin, primary cutaneous large B-cell lymphoma is proposed as the most appropriate term for this type of cutaneous lymphoma.

Jessner's lymphocytic infiltration of the skin. A clinical study of 100 patients.

Jessner's lymphocytic infiltration of the skin is a well-known but poorly understood disorder. Some doubt still exists about whether it is a single entity or a heterogeneous group that can pass into polymorphous light eruption, discoid lupus erythematosus, or even malignant lymphoma. Therefore, a large number of patients with lymphocytic infiltration of the skin (N = 100; 46 male, 54 female) were examined to elucidate these questions. We conclude that lymphocytic infiltration of the skin is a single entity. Progression into polymorphous light eruption, discoid lupus erythematosus, or lymphoma was not observed. However, this study shows that lymphocytic infiltration of the skin and polymorphous light eruption cases occur simultaneously in 1 patient. In this study the cases of 10 patients with this combination are reported. An effective but harmless therapy is yet unknown. Intermittent use of topical steroids can be useful but is not effective in many patients.

Aberrant immunophenotypes in mycosis fungoides.

Skin biopsy specimens from 40 patients with mycosis fungoides (MF) were examined by a selective procedure for the assessment of immunophenotypic deviation. In 19 cases (48%), aberrant phenotypes were detected. Type and degree of aberration differed greatly without apparent clinicopathologic correlation. Different phenotypes in the same patient occurring either simultaneously or during the course of the diseases were observed. Phenotypic aberration showed a statistically significant correlation with tumor stage MF, the large cerebriform tumor cell type, blast cell transformation, and diffuse dermal infiltration. In combination with longer-existing disease, more lymph node and visceral involvement and a higher mortality rate of MF in the aberrant group indicated an association with advanced disease. Its prognostic relevance for the individual patient, however, seemed limited because of the association of aberration and a long-lasting indolent course in many other patients. The assessment of phenotypic aberration formed a valuable contribution to the diagnosis of MF, especially in cases with little cellular atypia.

The diagnostic value of morphometry on blood lymphocytes in erythrodermic actinic reticuloid.

BACKGROUND: As the differential diagnosis of erythrodermic actinic reticuloid vs Sézary syndrome (SS) can be very difficult, we examined the value of the nuclear contour index (NCI) on blood lymphocytes as the criterion for differential diagnoses. The NCI is defined as the nuclear parameter divided by the square root of the nuclear area. Three different parameters were studied: mean NCI, percentage of cells with an NCI of 6.5 or greater, and the highest NCI. These indexes were studied on blood lymphocyte samples obtained from 10 patients with erythrodermic actinic reticuloid and were compared with the findings in 10 patients with other benign forms of erythroderma and in seven patients suffering from SS. RESULTS: The patients with erythrodermic actinic reticuloid differed significantly from the group with SS regarding the percentage of cells with an NCI of 6.5 or greater and the highest NCI, but not when the mean NCI was considered. All three parameters revealed nonsignificant results for erythrodermic actinic reticuloid compared with other benign forms of erythroderma. The group with SS differed significantly from the patients with other benign forms of erythroderma regarding all three parameters. By combining three morphometric criteria (mean NCI, > or = 5.5; > 30% lymphoid cells with an NCI of > or = 6.5; and highest NCI, > or = 11.5), all patients with erythrodermic actinic reticuloid or other benign forms of erythroderma and six of the seven patients with SS were correctly classified. CONCLUSION: Our data indicate that assessment of the NCI on peripheral blood lymphocytes is of value in the differential diagnosis of erythrodermic actinic reticuloid vs SS.

bcl-2 vs p53 protein expression and apoptotic rate in human nonmelanoma skin cancers.

BACKGROUND: A failure in the apoptotic response after severe genomic damage could facilitate cell transformation and tumor development, and a constitutive overexpression of either p53 or bcl-2 protein in nonapoptotic tumor cells could signify a defective bax-mediated apoptosis. OBJECTIVES: To investigate whether a negative correlation occurs between these 2 proteins in nonmelanoma skin cancer and whether overexpression of either protein is associated with a low rate of spontaneous apoptosis. DESIGN: Immunohistochemical study of nonmelanoma skin cancer archive material. SETTING: University referral center. PATIENTS: White patients with tumors on sun-exposed skin areas (ie, 17 basal cell carcinomas and 22 squamous cell carcinomas). MAIN OUTCOME MEASURES: Positivity for p53 and bcl-2 were scored semiquantitatively on 4 levels, and the percentages of apoptotic cells were determined. RESULTS: A significant negative correlation between p53 and bcl-2 expression was found in the basal cell carcinomas, but not in the squamous cell carcinomas, largely attributable to the low level of bcl-2 staining in the squamous cell carcinomas. Squamous cell carcinomas have a significantly higher number of apoptotic cells than basal cell carcinomas: 1.1% vs 0.6%, respectively. This spontaneous apoptosis decreases with increasing bcl-2 (in basal cell carcinoma), whereas it does not appear to be related to p53 level expression. CONCLUSIONS: These results indicate that a disturbance in either p53 or bcl-2 suffices to enhance skin tumor formation by suppressing apoptosis; bcl-2 appears to reduce the rate of spontaneous apoptosis, but an aberrant p53 expression does not, and this factor may solely affect the apoptosis from exogenous genotoxicity.