Home About us Contact
|
Home About us Contact | ||
|
|
||
Skin Carcinoma (skin + carcinoma)
Selected AbstractsSubclinical chronic lymphocytic leukaemia associated with a 13q deletion presenting initially in the skin: apropos of a caseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2006Abha Khandelwal Introduction:, B-cell chronic lymphocytic leukaemia (B-CLL) represents a low-grade B-cell lymphoproliferative disease that is the most common leukaemia in adults. The neoplastic cell is an autoreactive CD5 CD23 B lymphocyte. B-CLL may involve the skin, typically in the context of known disease. We present a case of subclinical B-CLL presenting initially in the skin. Case Report:, A 73-year-old male developed a lesion on his right cheek in April 2003 compatible with basal cell carcinoma. The re-excision specimen contained a well-differentiated atypical lymphocytic infiltrate consistent with B-CLL along with residual carcinoma. Subsequent laboratory studies revealed peripheral blood lymphocytosis with smudge cells. A diagnosis was made of Rai stage 0 CLL. Chromosomal studies on peripheral blood showed a deletion at 13q14.3. Excision of a second primary skin carcinoma revealed a squamous cell carcinoma in association with B-CLL that was identical to his previously diagnosed skin involvement. Conclusion:, This case identifies a cutaneous presentation of subclinical B-CLL. There are two prior reports describing B-CLL presenting initially in the skin. In one case, the infiltrates were incidental on a re-excision specimen. The second report suggests 16% of B-CLL patients have cutaneous manifestations as the first sign of disease. [source] Ets-1 immunohistochemical expression in non-melanoma skin carcinomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2004Connie A. Keehn Background:, Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in non-melanoma skin carcinomas. Design:, A series of 26 primary cutaneous skin lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle Upon Tyne, England, UK) was scored by an average of the mean labeling intensity (MLI), where no nuclear staining = 0, weak nuclear staining = 1, moderate nuclear staining = 2, and strong nuclear staining = 3. Results:, All basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC) cases exhibited negative nuclear staining, for an average MLI of 0. Keratoacanthomas, squamous cell carcinoma in situ (SIS), and well-differentiated squamous cell carcinomas (SCCs) exhibited negative to weak nuclear staining, for an average MLI of 0.4 ± 0.3. Moderately differentiated SCCs exhibited moderate nuclear staining, for an average MLI of 1.8 ± 0.6. Poorly differentiated SCCs and metastatic SCCs exhibited very strong nuclear staining, with an average MLI of 2.8 ± 0.2. Conclusions:, Ets-1 is not expressed in cutaneous BCC or MCC and is weakly expressed in SIS and forms of well-differentiated SCC. Although the intensity of Ets-1 immunostaining distinguished between well-differentiated and poorly differentiated SCC (p < 0.0001), it failed to discriminate between in situ and well-differentiated SCCs. The preliminary data suggests Ets-1 may be important in the pathogenesis of invasive SCC. [source] Protein expression profiling of glutathione S -transferase pi null mice as a strategy to identify potential markers of resistance to paracetamol-induced toxicity in the liverPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 2 2003Neil R. Kitteringham Abstract GST pi (GSTP) is a member of the glutathione S -transferase (EC 2.5.1.18; GST) family of enzymes that catalyse the conjugation of electrophilic species with reduced glutathione and thus play an important role in the detoxification of electrophilic metabolites. Deletion of GSTP in mice has previously been shown to lead to enhanced susceptibility to chemical-induced skin carcinoma, consistent with its known metabolic functions. A decreased susceptibility to paracetamol hepatotoxicity has also been observed, which has not been fully explained. One possibility is that deletion of the GSTP gene locus results in compensatory changes in other proteins involved in defence against chemical stress. We have therefore used complementary protein expression profiling techniques to perform a systematic comparison of the protein expression profiles of livers from GSTP null and wild-type mice. Analysis of liver proteins by two-dimensional electrophoresis confirmed the absence of GSTP in null mice whereas GSTP represented 3,5% of soluble protein in livers from wild-type animals. There was a high degree of quantitative and qualitative similarity in other liver proteins between GSTP null and wild-type mice. There was no evidence that the absence of GSTP in null animals resulted in enhanced expression of other GST isoforms in the null mice (GST alpha, 1.48%, GST mu, 1.68% of resolved proteins) compared with the wild-type animals (GST alpha, 1.50%, GST mu, 1.40%). In contrast, some members of the thiol specific antioxidant family of proteins, notably antioxidant protein 2 and thioredoxin peroxidases, were expressed at a higher level in the GSTP null mouse livers. These changes presumably reflect the recently described role of GSTP in cell signalling and may underlie the protection against paracetamol toxicity seen in these animals. [source] Calcitriol treatment improves methyl aminolaevulinate-based photodynamic therapy in human squamous cell carcinoma A431 cellsBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2009E. Cicarma Summary Background, Photodynamic therapy (PDT) using methyl aminolaevulinate (MAL) provides a new, approved method for treatment of skin cancer and its precursors. However, MAL-based PDT is not very efficient for poorly differentiated skin carcinoma. Thus, novel strategies to enhance the PDT effect are needed. Objectives, In order to improve the efficacy of MAL-based PDT, we investigated the effect of adding calcitriol, a prodifferentiation hormone, to human squamous cell carcinoma A431 cells in vitro. Methods, A short course (24 h) of calcitriol pretreatment was applied in A431 cells, and, subsequently, MAL-induced protoporphyrin IX (PpIX) was measured. Results, Calcitriol pretreatment of the cells elevated their PpIX levels. Furthermore, the cell damage after exposure to blue light was significantly higher in calcitriol-treated cells. Increased photoinactivation correlated with higher levels of PpIX in the calcitriol-pretreated cells. Conclusions, Calcitriol enhances MAL-based PDT in A431 cells. [source] Diagnostic value and prognostic significance of protein S-100,, melanoma-inhibitory activity, and tyrosinase/MART-1 reverse transcription-polymerase chain reaction in the follow-up of high-risk melanoma patientsCANCER, Issue 7 2003Claus Garbe M.D. Abstract BACKGROUND Cutaneous melanoma is the most aggressive form of skin carcinoma in humans, frequently with a rapid progression of disease. To detect early developing metastasis, laboratory tests to determine levels of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) form part of the regular follow-up, but often cannot discover recurrent disease at a sufficiently early stage. METHODS To evaluate the diagnostic accuracy of protein S-100, (S-100,), melanoma-inhibitory activity (MIA), LDH, AP, and tyrosinase/MART-1 reverse transcription-polymerase chain reaction (RT-PCR), the authors included 296 consecutive AJCC Stage II or III clinically disease-free melanoma patients. Follow-up examinations were performed every 3 months and blood samples were drawn to determine the levels of these tumor markers. RESULTS Metastasis occurred in 41 of the 296 patients during a median follow-up period of 19 months (range, 1,33 months). The sensitivity to detect new metastases was 29% for protein S-100,, 22% for MIA, 2% for LDH, 17% for AP, and 24% for RT-PCR. The diagnostic accuracy was best for MIA (86%) and S-100, (84%), whereas AP (79%), LDH (77%), and RT-PCR (72%) demonstrated lower values. Elevated values of S-100, and MIA during follow-up examinations were associated with decreased survival rates in the further course of the disease, but pathologic findings of the other tumor markers showed no prognostic impact. CONCLUSIONS To the authors' knowledge, the current study is the first comparison of the diagnostic accuracy of currently available tumor markers in the follow-up of high-risk melanoma patients. Protein S-100, and MIA demonstrated a higher sensitivity, specificity, and diagnostic accuracy in the diagnosis of newly occurring metastasis compared with to the tumor markers AP, LDH, and RT-PCR diagnostics. Therefore, the tumor markers S-100, and MIA may be useful in the follow-up of disease-free Stage II and III melanoma patients. Cancer 2003;97:1737,45. © 2003 American Cancer Society. DOI 10.1002/cncr.11250 [source] Predictors of skin self-examination performanceCANCER, Issue 1 2002June K. Robinson M.D. Abstract BACKGROUND Skin self-examination (SSE) may reduce the death rate from melanoma by as much as 63%. Enhancing SSE performance may reduce mortality and morbidity. This study determined predictors of SSE performance in a population of individuals who were at risk of developing melanoma or nonmelanoma skin carcinoma (NMSC). METHODS Patients (n = 200) were asked about their knowledge of the warning signs, their sense of the importance of SSE to them, their attitude about and confidence in their ability to perform SSE, and their impression of their partner's comfort and ability with assisting in the skin examination. The interval since last skin examination, the number of physician visits (nondermatologist and dermatologist), the number and type of skin malignancies, the time since initial diagnosis, the number of skin biopsies, and health insurance status were determined from the medical records for the prior 3 years. RESULTS Seventy percent of participants performed SSE. The three strongest predictors of SSE performance were attitude, having dermatology visits with skin biopsies and at least one skin carcinoma in the previous 3 years, and confidence in performance (P = 0.0001). Other predictors of SSE performance were perceived risk (P = 0.0001), knowledge (P = 0.004), and younger age (P = 0.045). CONCLUSIONS Annual skin examination by physicians and monthly SSE by patients reinforce one another in promoting early detection. In this high-risk population, the dermatologist reinforced SSE performance by biopsy of skin lesions that were skin malignancies. People have intimate knowledge of their own skin and bear the consequences for failure to detect and treat skin carcinoma early; thus, monthly SSE becomes relevant as a personal health-promotion habit. Cancer 2002;95:135,46. © 2002 American Cancer Society. DOI 10.1002/cncr.10637 [source] Angiogenesis and skin carcinomas with skull base invasion: a case,control study,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2004Claudio R. Cernea MD Abstract Background. Some skin carcinomas may be very aggressive. Intensity of angiogenesis, measured by intratumoral vessel density using expression of CD34, has been associated with tumor aggressiveness. In this study, the expression of CD34 in basal cell carcinomas ( BCCs) and squamous cell carcinomas (SCCs) with skull base invasion was compared with that in tumors with good outcome. Methods. Expression of CD34 was graded as mild, moderate, and intense, in 24 BCCs and 11 SCCs with skull base invasion. The control group included 23 BCCs and 10 SCCs. Results. Intense expression of CD34 was noted in 25.00% of BCCs with skull base invasion, compared with 4.35% in the control group (p = .058). Regarding SCCs, intense expression of CD34 was found in 54.55% of aggressive tumors, compared with 10.00% in the control group (p = .133). Conclusions. A trend toward denser microvascular angiogenesis was observed in both BCCs and SCCs with skull base invasion compared with less aggressive controls. © 2004 Wiley Periodicals, Inc. Head Neck26: 396,400, 2004 [source] Ets-1 immunohistochemical expression in non-melanoma skin carcinomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2004Connie A. Keehn Background:, Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in non-melanoma skin carcinomas. Design:, A series of 26 primary cutaneous skin lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle Upon Tyne, England, UK) was scored by an average of the mean labeling intensity (MLI), where no nuclear staining = 0, weak nuclear staining = 1, moderate nuclear staining = 2, and strong nuclear staining = 3. Results:, All basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC) cases exhibited negative nuclear staining, for an average MLI of 0. Keratoacanthomas, squamous cell carcinoma in situ (SIS), and well-differentiated squamous cell carcinomas (SCCs) exhibited negative to weak nuclear staining, for an average MLI of 0.4 ± 0.3. Moderately differentiated SCCs exhibited moderate nuclear staining, for an average MLI of 1.8 ± 0.6. Poorly differentiated SCCs and metastatic SCCs exhibited very strong nuclear staining, with an average MLI of 2.8 ± 0.2. Conclusions:, Ets-1 is not expressed in cutaneous BCC or MCC and is weakly expressed in SIS and forms of well-differentiated SCC. Although the intensity of Ets-1 immunostaining distinguished between well-differentiated and poorly differentiated SCC (p < 0.0001), it failed to discriminate between in situ and well-differentiated SCCs. The preliminary data suggests Ets-1 may be important in the pathogenesis of invasive SCC. [source] INK4a-ARF mutations in skin carcinomas from UV irradiated hairless miceMOLECULAR CARCINOGENESIS, Issue 4 2004N. Soufir Abstract To characterize further the role of the INK4a-ARF locus in the multistep process of skin carcinogenesis, we performed a mutational analysis of this locus in skin lesions from hairless mice either irradiated with UVB alone or with a solar simulator delivering UVA,+,B. INK4a-ARF mutations were present in five of 57 squamous cell carcinomas (9%), but no mutation was detected in precancerous lesions. All mutations were C:G,>,T:A transitions located at dipyrimidic sites, the hallmark of UVB mutagenesis. Three mutations affected only the p19ARF reading frame, whereas two mutations affected only the p16INK4a transcript. This study demonstrates for the first time UV-induced mutations of INK4a-ARF that occur in a small percentage in late stages skin tumors. © 2004 Wiley-Liss, Inc. [source] UV-induced Immunosuppression in the Balance,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2008Frank R. De Gruijl Around 1980, experiments with hairless mice showed us that UV-induced actinic keratoses (AK) and ensuing skin carcinomas did not arise independently: the rate of occurrence in one skin area was increased considerably if AKs had already been induced separately in another distant skin area, i.e. a systemic effect. The ground laying work of Margaret Kripke in the 1970s provided a fitting explanation: UV-induced immunosuppression and tolerance toward the UV-induced tumors. From Kripke's work a new discipline arose: "Photoimmunology." Enormous strides were made in exploring and expanding the effects from UV carcinogenesis to infectious diseases, and in elucidating the mechanisms involved. Stemming from concerns about a depletion of the ozone layer and the general impact of ambient UV radiation, the groups I worked in and closely collaborated with explored the anticipated adverse effects of UV-induced immunosuppression on healthy individuals. An important turning point was brought about in 1992 when the group of Kevin Cooper reported that immunosuppression could be induced by UV exposure in virtually all human subjects tested, suggesting that this is a normal and sound physiological reaction to UV exposure. This reaction could actually protect us from illicit immune responses against our UV-exposed skin, such as observed in idiopathic polymorphic light eruption. This premise has fruitfully rekindled the research on this common "sun allergy," affecting to widely varying degrees about one in five Europeans with indoor professions. [source] Leukaemia inhibitory factor and interleukin-8 expression in nonmelanoma skin cancersCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2001Jacek C. Szepietowski Leukaemia inhibitory factor (LIF) and interleukin (IL)-8 possess activities which may contribute to the development of carcinomas. LIF can stimulate proliferation of some tumour cell lines and IL-8 is angiogenic. Using semiquantitative reverse-transcription polymerase chain reaction (RT,PCR), we measured the expression of LIF and IL-8 mRNA in cultured normal keratinocytes (NKC) and the malignant carcinoma cells lines A431, SiHa, HeLa, and in biopsies of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin. Protein expression for LIF was assessed by immunohistochemistry in the biopsies. LIF mRNA expression was increased significantly (P < 0.01) in all carcinoma lines, except SiHa, compared with NKC but the IL-8 mRNA expression in carcinoma cell lines was similar to that in NKC. Expression of LIF mRNA was elevated in BCC and SCC compared with normal skin, but a significant difference was observed only between SCC and normal skin (P < 0.01). Both BCC and SCC showed significantly greater expression of IL-8 compared with normal skin (P < 0.01). There was no correlation between LIF and IL-8 mRNA expression either in BCCs or in SCCs. Immunoreactivity for LIF was absent throughout BCC and SCC, however, normal epidermis surrounding the tumour stained positive, as in normal skin. These data may suggest a role for LIF and IL-8 in the development of skin carcinomas, but without co-ordinate regulation of these two cytokines in this process. [source] | ||||||||||||||||||||||