Oncoplastic breast surgery: comprehensive review.

Breast cancer is the most common female cancer in Western populations, affecting 12.5% of women, with 1.38 million patients per year. Breast-conserving surgery followed by postoperative radiotherapy replaced the radical and modified-radical procedures of Halsted and Patey as the standard of care for early-stage breast cancer once the overall and disease-free survival rates of breast-conserving surgery were demonstrated to be equivalent to those of mastectomy. However, excision of >20% of breast tissue, low or centrally located cancer, and large-sized breasts with various grades of breast ptosis, result a in unacceptable cosmetic outcomes. Oncoplastic breast surgery evolved from the breast-conserving surgery by broadening its general indication to achieve wider excision margins without compromising on the cosmetic outcomes. Thus, oncoplastic breast surgery can be defined as a tumor-specific immediate breast reconstruction method that applies aesthetically derived breast reduction techniques to the field of breast cancer surgery and allows for higher volume excision with no aesthetic compromise. However, contralateral breast symmetrization should be regarded as an intrinsic component of the oncoplastic surgery. The main procedures involved are volume-displacement or volume-replacement techniques, which depend on breast size and cancer size/location. Volume-displacement or reshaping procedures apply the plastic surgery principles to transpose a dermo-glandular flap of breast tissue into the defect site, while volume-replacement techniques use autologous tissues to replace the volume loss that follows tumor resection. Furthermore, these procedures are more complex and time-consuming than those involved in breast-conserving surgery. Based on current literature, the authors analyze the different techniques and indications of the oncoplastic breast surgery, determining its complication rate, in order to help both surgeons and their patients in the decision-making stage of breast reconstruction.

Surgical prevention and treatment of lymphedema after lymph node dissection in patients with cutaneous melanoma.

Despite the development of minimal access dissection techniques, use of superficial groin dissection alone, and other recommendations to reduce morbidity in melanoma treatment, the incidence of lymphedema is still significant. The purpose of the current study was to assess the efficacy of microsurgical methods to limit the morbidity of inguinal lymphadenectomy. We conducted a retrospective review of patients who underwent groin dissection for melanoma treatment from February 2006 to April 2009. A total of 59 melanoma patients with positive groin lymph nodes comprised 18 patients (T-group) with melanoma in the trunk and 41 patients (E-group) who had melanoma in an extremity and currently have lymphedema. The T-group patients underwent primary prevention of lymphedema with microsurgical lymphatic-venous anastomoses (LVA) performed simultaneously with groin dissection. The E-group patients underwent LVA to treat the secondary lymphedema after an accurate oncological and lymphological assessment. Limb volume measurements and lymphoscintigraphy were performed pre- and postoperatively to assess short and long term outcome. No lymphedema occurred after microsurgical primary preventive approach in the T- group. Significant (average 80% reduction of pre-op excess volume) reduction of lymphedema resulted after microsurgical treatment for secondary leg lymphedema. Post-operative lymphoscintigraphy in 35 patients demonstrated patency of microsurgical anastomoses in all cases with an average follow-up of 42 months. Study results demonstrate that microsurgical LVA primary prevention prevented lymphedema after inguinal lymphadenectomy in the T-group patients. In addition, lymphatic-venous multiple anastomoses proved to be a successful treatment for clinical lymphedema with particular success if treated at the early stages.

General surgery, translational lymphology and lymphatic surgery.

A wide clinical experience in General Surgery has brought about a remarkable knowledge about lymphatic disorders both primary and secondary ones. Diagnostic and histopathological studies of lymphatic diseases allowed to better understand etiological aspects and pathophysiological mechanisms responsible of complex clinical features correlated to lymphatic dysfunctions. Translational lymphologic basic and clinical researches permitted to improve therapeutical approaches both from the medical and surgical point of view. Thus, strategies of treatment were proposed to prevent lymphatic injuries, to avoid lymphatic complications and to treat lymphatic diseases early in order to be able even to cure these pathologies.

A comparative study of proliferation and hepatic differentiation of human adipose-derived stem cells.

Human adipose-derived stem cells possess a lot of stem cell characteristics, so they may be considered a source of stem cell population. On the basis of that, we have investigated the hepatic potential of adipose-derived stem cells, obtained from liposuction, following two differentiation protocols. In the first procedure, medium was supplemented with epidermal growth factor (EGF), basic fibroblast growth factor, hepatocyte growth factor (HGF) and nicotinamide; the second involved the addition of factors such as dexametasone, EGF, insulin-transferrin-sodium selenite, HGF, dimethyl sulfoxide and oncostatin. In parallel, we carried out our study in the Hep G2 cell line, as human hepatic differentiated in vitro model. Immunocytochemical analysis and RT-PCR were performed using hepatic markers to evaluate cell differentiation. DNA content, MTT test and carboxyl fluorescein succinimidyl ester staining were carried out to evaluate cell proliferation. We reported the evidence of basal hepatic marker in undifferentiated adipose-derived stem cells, which confirmed their multipotency. A strong expression of albumin and alpha-fetoprotein was observed in hepatic-induced adipose-derived stem cells following both differentiation procedures. Morphological aspects of the two types of hepatic adipose-derived stem cells were alike. Proliferation index suggested that the first differentiation procedure promoted better growth than the second. These preliminary findings suggest adipose-derived stem cells may be induced into hepatic lineage, and the most significant difference between the two standard differentiation procedures concerns proliferation rate. This aspect is to be considered when adipose-derived stem cells are employed in research and clinical studies.

In vitro polydeoxyribonucleotide effects on human pre-adipocytes.

OBJECTIVES: Adipose tissue is the most abundant and accessible source of adult stem cells. Human processed lipoaspirate contains pre-adipocytes that possess one of the a characteristic pathways of multipotent adult stem cells and are able to differentiate in vitro into mesenchymal and also neurogenic lineages. Because stem cells have great potential for use in tissue repair and regeneration, it would be significant to be able to obtain large amounts of these cells in vitro. As demonstrated previously, purine nucleosides and nucleotides mixtures can act as mitogens for several cell types. The aim of this study was to evaluate the effects of polydeoxyribonucleotides (PDRN), at appropriate concentrations, on human pre-adipocytes grown in a controlled medium, also using different passages, so as to investigate the relationship between the effect of this compound and cellular senescence, which is the phenomenon when normal diploid cells lose the ability to divide further. MATERIALS AND METHODS: Human pre-adipocytes were obtained by liposuction. Cells from different culture passages (P6 and P16) were treated with PDRN at different experimental times. Cell number was evaluated for each sample by direct counting after trypan blue treatment. DNA assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test were also carried out in all cases. RESULTS AND CONCLUSIONS: PDRN seemed to promote proliferation of human pre-adipocytes at both passages, but cell population growth increased in pre-adipocyte at P16, after 9 days as compared to control. Our data suggest that PDRN could act as a pre-adipocyte growth stimulator.

Characterization and induction of human pre-adipocytes.

Human processed lipoaspirate is a source of multipotent adult stem cells that are able to differentiate between mesenchymal and neurogenic lineage. We characterized PLA cells by cytometry and then they were cultured to induce differentiation into myogenic and neurogenic lineage. Lipoaspirates were digested with collagenase to obtain the pellet, which was labelled with anti-CD44, anti-CD45, and anti-CD90. We used BD FACS Calibur flow cytometer to acquire cellular events. Some cells were cultured at 37 degrees C and 5% CO(2) in neurogenic or myogenic medium and analysed by immunocytochemistry, using Neuron specific enolase, Vimentin, Glial fibrillary acidic protein, Tau, MAP2 to confirm neurogenic differentiation, MyoD1, Myosin heavy chain, Actin smooth muscle, vimentin to confirm myogenic differentiation. The cytometry results suggest that a part of the cells are of a mesenchymal origin, among which there are progenitor endothelial cells and leucocytes. Microscopy observation already reveals neuronal morphology and longitudinal multinucleated cells compared to control cells. Neurogenic cells only express NSE (early neuronal progenitor marker), but not GFAP, Tau, MAP2 (mature neuron and glial markers); myogenic cells are positive for MyoD1 and Myosin heavy chain. This demonstrates that lipoaspirate cells are capable of differentiating in vitro over a short period of time, and could be employed in biological and clinical research, like mesenchymal adult stem cells.

Characterization of multipotent cells from human adult hair follicles.

Recent works demonstrated the presence of a multipotent epithelial cell population in the bulge region of adult human hair follicles. These cells can be cultured in vitro, thus leading to the preparation of dermal-epidermal substitutes which are applicable in the treatment of burns and ulcers. We evaluated the main marker expression in cells obtained from stripped human hair follicles. A pool of hair follicles were incubated at 37 degrees C and 5% CO(2) in a growth medium. The cells were then labelled with antibodies (anti-CD34, anti-CD38, anti-CD45, anti-CD90, anti-CD133, anti-CD146) and analysed by cytometry. We also used hair follicles for immunohistochemical studies, employing antibodies such as CD34, Actin Smooth Muscle, Filaggrin, Desmin, Vimentin, Glial Fibrillary Acidic Protein, Ki-67, PanCytokeratin, CK15, CK19. The cytometry results revealed that a part of bulge cells were CD34+ (1-2%). CD34+ population comprises both large, CD45-, CD133-, CD146- cells and small, CD45+, CD133+, CD146+ cells. Thus, a part of CD34+ cells present a mature endothelial marker (CD146). An expression of the proliferation marker Ki-67 and the stem cell marker CD34 is present in the follicle bulge region. In conclusion, we observed that the stripped hair follicle has the same multipotent cell population as adult and fetal scalp hair follicles.

[Computer-based preoperative planning for breast reconstruction in the woman with unilateral breast hypoplasia]. / Pianificazione computerizzata per la ricostruzione mammaria in donne affette da ipoplasia mammaria unilaterale.

BACKGROUND: Aim of this paper is to describe a computer program which can provide objective and quantitative data useful for the selection of the proper implant in order to obtain the symmetry with the contralateral breast in case of unilateral breast reconstruction by tissue expansion, especially for the surgeon without experience or for the occasional operator. METHODS: Our C++ program provides the final implant volume using the measurements of the semi-circumference and projection of the contralateral breast performed on the supine patient. The aim is the symmetry of the two breasts. RESULTS: According to our experience in breast reconstruction by tissue expanders, this program allows non invasive and simple measurements of the breast volume, useful to obtain the mammary symmetry. CONCLUSIONS: In case of breast reconstruction by tissue expansion, the preoperative evaluation is usually based on the surgeon's experience and on empirical observations without knowing the correct volume to reach. For this reason our program is useful to know the necessary volume for breast reconstruction, and therefore it allows the surgeon to obtain a better plastic result.

[Experimental model for the evaluation of topical application of a solution to help myocutaneous flap transposition]. / Modèle expérimental pour l'évaluation d'une solution topique améliorant la survie des lambeaux myocutanés.

The aim of this article is the evaluation of the topical application of a solution of hydrogen peroxide (H2O2) 8% and dimethyl sulphoxide (DMSO) 50% in order to reduce ischaemic failure in random skin flaps. This study was performed using a rabbit model. Two parallel, cephalad-based para-midline random cutaneous flap (10 cm x 2.5 cm) were elevated and resutured in place on the dorsum of 40 New Zealand rabbits. The 80 flaps thus obtained were then randomly divided into one control group and three experimental groups of 20 flaps each. Flaps from the control group (group A) were topically treated with saline, while flaps from experimental group B were treated with H2O2 8%, flaps from experimental group C with DMSO 50%, and flaps from experimental group D with a solution of 50% DMSO + 8% H2O2. Each solution was topically applied, 20 cc per three times a day, on the flaps for seven days, starting on the immediate postoperative period. Transcutaneous oxygen tension (Ptc O2) measurements were carried out in all flaps, 72 h after flap elevation. The percentage of surviving skin area of each flap was determined by planimetry 7 days after flap elevation. The mean surviving area of the group A (control) flaps was 71%. The mean surviving area of the group B (H2O2-treated) flaps was 72%. The mean surviving area of the group C (DMSO-treated) flaps was 76%, and that of the group D (DMSO + H2O2-treated) flaps was 92%. While no statistically significant differences were found between the survival rates of both the flaps treated with H2O2 or DMSO alone and that of the control group, the mean surviving rate of the DMSO + H2O2 treated flaps (+20%) was statistically higher than that of the control flaps. Similarly, a statistically significant difference has been found between the mean Ptc O2 values of the DMSO + H2O2 flaps and those of the other three groups of flaps.

[Evaluation of the tolerability of Hydrogel breast implants: a pilot study]. / Studio pilota per la valutazione della tollerabilità delle protesi tipo hydrogel.

BACKGROUND: During the 90s the widely publicised controversy regarding the use of silicone gel breast implants stimulated research into alternative alloplastic filling materials. In this context, a new type of breast implant, containing Carboxymethylcellulose at 3.7% in the form of Hydrogel, was introduced into the European market. METHODS: A preliminary pilot study was carried out to evaluate the tolerability and reliability of breast implants pre-filled with Hydrogel. A group of 12 consecutive patients was recruited for this purpose and underwent plastic surgery for breast augmentation or reconstruction (20 implants) at the Department of Plastic and Reconstructive Surgery at the University of Genoa between December 1996 and October 1997. All patients were then followed up for a minimum of 3.5 years. The mean age of patients was 50 years and ranged from 28 to 67 years old. After surgery the patients were examined at 4 weeks (evaluation of any immediate complications), 3 months, 6 months and 1 year (evaluation of any delayed complications). RESULTS: No immediate complications were reported in any patient. After 3.5 years of follow-up, the degree of capsular contraction according to Baker in these patients varies between 1 and 2. In general, the implants were very soft to touch even some time after surgery, above all in patients undergoing breast augmentation. Four implants (20%) were removed from 3 patients for reasons unconnected to the implants themselves (because of neoplasm in one case and due to inadequate volume in the other two patients). No case of rupture has been reported. CONCLUSIONS: This pilot study appears to confirm the validity of implants prefilled with Hydrogel in reconstructive or cosmetic breast surgery. A larger population and longer periods of minimum follow-up are obviously required to confirm these results over the long term.

[Computer-aided preoperative planning of tissue expansion]. / Pianificazione preoperatoria dell'espansione tissutale supportata dal computer.

OBJECT: The aim of this paper is to introduce a computer program developed to provide objective and quantitative data useful to provide proper expander selection when a rectangular tissue expander has to be used. METHODS: The program has been developed to calculate the volume of a rectangular tissue expander to obtain the exact amount of yield necessary to allow for reconstruction of a determined defect. The only data to be supplied are the length and the width of the defect to be reconstructed. RESULTS: The accuracy of the results obtained by the computer program was tested clinically comparing preoperative data with volume measurements obtained at the end of the expansion procedure. In our study the resulting data did not show any statistically significant difference (p<0,05) between the two groups. CONCLUSIONS: In our opinion, although its use is not aimed at replacing clinical judgment based on experience and careful observation, this program may be considered a simple and useful adjunct for the inexperienced surgeon (or the occasional operator) planning to use a rectangular tissue expander.

[Minimally-invasive endoscopic transthoracic sympathectomy of the upper limbs. A new method]. / Denervazione simpatica mini-invasiva degli arti superiori. Nuova metodica.

OBJECTIVE: Indications for endoscopic transthoracic upper dorsal sympathectomy are axillary and palmar hyperhidrosis, upper extremities ischemia (due to, e.g., Raynaud s disease), and upper extremities causalgia. METHODS: At present, this methodology relies on (at least) double trocar insertion (per side) and/or carbon dioxide insufflation. Thus, although this approach, compared with the traditional open sympathectomy techniques, it guarantees the smallest number of postoperative complications, it still determines a certain amount of postoperative discomfort as well as a risk of complications related to carbon dioxide insufflation, as intraoperative profound bradycardia and hypotension due to mediastinal shift, and postoperative subcutaneous emphysema. From December 1995, we are using a minimally-invasive endoscopic transthoracic sympathectomy technique, performed by a single-entry specifically modified thoracoscope and without the need for carbon dioxide insufflation, with the aim to reduce the drawbacks associated with the above-mentioned currently adopted endoscopic techniques. After general anesthesia with double-lumen endotracheal tube, with the patient placed in a half-sitting position with both arms abduced to 90 degrees, a 1 cm incision is performed, along the midclavear line (in male patients) or the anterior axillary line (in female patients), in the second or third intercostal space. RESULTS: The effects of sympathectomy are immediate, and the patients wake up with warm and dry hands and axillae. CONCLUSIONS: In personal opinion, this single-entry technique, compared with other reported approaches, should minimize any damage to the intercostal neurovascular bundle, while avoiding the complications connected with carbon dioxide insufflation.

[Computer planning for postmastectomy breast reconstruction by tissue expansion]. / Pianificazione computerizzata per la ricostruzione mammaria postmastectomia mediante espansione tissutale.

Aim of this paper is to present a computer program able to provide objective and quantitative data useful to guarantee the selection of the proper implant in order to obtain symmetry with the contralateral breast, in case of unilateral breast reconstruction by tissue expansion, especially for surgeons without experience or for occasional operators. Our C++ program provides the final implant volume using the measurements of the semi-circumference and projection of the contralateral breast performed on the supine patient. The aim is the symmetry of the two breasts. According to personal experience in breast reconstruction by tissue expanders, this program allows non invasive and simple measurements of the breast volume, useful to obtain the mammary symmetry. In case of breast reconstruction by tissue expansion, the preoperative evaluation is usually based on the surgeon experience and on the empirical observation without knowing the correct volume to reach. Since this program is useful to know the precise necessary volume for breast reconstruction, it allows the surgeon to obtain a better plastic result.

A single genetic origin for the G101W CDKN2A mutation in 20 melanoma-prone families.

Germline mutations within the coding region of CDKN2A have been observed in affected members of melanoma-prone families. G101W is the most common CDKN2A missense mutation identified to date. It has been reported in several families from around the world, with a particularly high occurrence in France and Italy. Given the frequency of this mutation, we were interested in determining whether the mutation resulted from a single origin or represented a mutational hotspot in the CDKN2A gene. In addition, given the geographical distribution of the mutation, we examined the date of origination of the mutation and its migratory spread. We examined 10 families from Italy, 4 families from the United States, and 6 families from France with the G101W mutation. The following eight markers were employed for the haplotype analysis: IFNA, D9S736, D9S1749, D9S942, D9S1748, D9S1604, D9S171, and D9S126. Our findings showed no significant evidence for mutational heterogeneity, suggesting that all studied families derived from a single ancestral haplotype on which the mutation arose. Using maximum-likelihood methods, we estimated the mutation to have arisen 97 generations ago (1-LOD-unit support interval 70-133 generations) providing some explanation for the wide geographical spread of this common mutation, particularly in southwestern Europe. The presence of a founder mutation in a defined geographic area can facilitate carrier detection and genetic counseling and can provide an opportunity to study disease penetrance and the effect of environmental factors on the background of a common genetic susceptibility.

Quantitative benefits provided by acute tissue expansion: a biomechanical study in human cadavers.

The aim of this study was to test the ex vivo biomechanical properties of acutely expanded cutaneous flaps to quantitatively assess the efficacy of intraoperative tissue expansion. A total of 14 fresh male cadavers were used for the study. In each cadaver, a rectangular (15 x 8 cm), proximally based flap was designed on each side of the body, in three different locations: lateral arm, anterior thorax, anterior thigh. In each cadaver, one randomly selected flap per each body region underwent acute-intermittent expansion, whereas the contralateral flap served as control. The biomechanical properties (stress/strain ratio, mean stiffness) of both expanded and control flaps were then assessed by means of a dynamometer and a force-transducer. The obtained data showed that the biomechanical benefits provided by acute tissue expansion were statistically different (P< 0.05) from those obtained by simple subcutaneous undermining. While no changes of length have been observed in the acutely expanded skin flaps as compared to control cutaneous flaps, a statistically significant gain in the compliance of the former has been recorded as compared to the biomechanical behaviour of the latter.

[Intraoperative expansion of scalp flaps. Quantitative assessment]. / Espansione intraoperatoria di lembi di scalpo. Valutazione quantitativa.

BACKGROUND: The aim of this study was to test the ex-vivo biomechanical properties of acutely expanded scalp flaps, in order to quantitatively assess the efficacy of acute scalp expansion. METHODS: A total of 14 fresh male cadavers were used for the study. In each cadaver, a rectangular (4 x 10 cm), laterally-based flap was designed on each side of the scalp, starting from the superior margin of the external auditory canal. One randomly-selected flap per each scalp underwent acute-intermittent expansion (3-minute expansion-3-minute rest cycle per three times with the maximal expansion achievable), while the contralateral flap served as control. After the expansion process, the acutely-expanded flaps were measured to assess if the applied biomechanical stress have determined any changes in their dimensions. The biomechanical properties (stress/strain ratio, mean stiffness) of both expanded and control flaps were then assessed by means of a dynamometer and a force-transducer. RESULTS: The obtained data showed that the biomechanical benefits provided by acute scalp expansion were not statistically different (p < 0.05) from those obtained by simple subgaleal undermining. Neither any change of length nor any gain in the compliance have been observed in the acutely-expanded flaps as compared to control scalp flaps. CONCLUSIONS: In our opinion, a possible explanation (to be further validated) for the lack of effect of acute scalp expansion might be that inelastic galea aponeurotica did not allow the mechanical creep to exploit the inherent elastic properties of the overlying scalp skin.

Characterization of ligurian melanoma families and risk of occurrence of other neoplasia.

Germline mutations impairing the p16(INK4)-function have previously been demonstrated to be responsible for genetic predisposition in at least one half of melanoma-prone kindreds of North European origin. Familial melanoma kindreds have also been found to present an increased risk of pancreatic cancer and other cancers, but results relative to more common neoplasias incidence, in particular, are heterogeneous. We report here a clinical-epidemiological study, including the presence of additional neoplasias, in 14 apparently unrelated kindreds coming from a small geographic region of Northern Italy (Liguria), having therefore lived for generations in similar environmental conditions. We identified the common p16 missense mutation (Gly101Trp) reported in several previously studied kindreds, in 7 of 14 families, whereas the remaining 7 families had no detectable mutations in the coding region of p16 gene. Median age at diagnosis and other melanoma features were studied. When compared with the expected figures, based on regional incidence rates, a significant excess of pancreatic cancer, with 4 cases diagnosed, and of breast cancer, with 7 cases, was observed. The 7 families without apparent CDKN2A involvement were also negative for hot-spot exon 2 mutation of CDK4. Environmental factors do not appear to play a role in the excess of non-melanoma neoplasia in our families, as somewhat substantiated by the control group, composed of spouses and members of non-affected branches; they do not reveal any increased cancer incidence compared with the general population. Furthermore, given the proven significance of interaction between the melanoma susceptibility gene and the propensity to sunburns and other environmental risk factors, our results, obtained from a small but homogeneous sample, may have important implications for further risk assessment studies.

Topical application of DMSO as an adjunct to tissue expansion for breast reconstruction.

The aim of this study was to evaluate the effectiveness of topical 60% dimethyl sulphoxide (DMSO) prior to tissue expansion for breast reconstruction in reducing expander pressure and length of treatment. Forty patients undergoing immediate breast reconstruction with tissue expanders following modified radical mastectomy were consecutively divided into two groups of 20 subjects each: group A (control) and group B (experimental). Patients from group A underwent traditional tissue expansion, while, to patients of group B, before each filling session, topical 60% DMSO was applied to the skin overlying the expander by soaking-wet surgical sponges left in place for 30 min. The average inflated volume was 395 cc (range 250-580 cc) in group A, and 410 cc (range 240-620 cc) in group B; no statistically significant difference was found between these values. A statistically significant difference was found between the expansion time of group A (mean 6 sessions; range 4-10 sessions with one filling session per week) and group B (mean 4 sessions; range 2-6 sessions with one filling session per week). A statistically significant difference was also found between the average inflated volume per session of group A (90 cc; range 60-130 cc) and group B (120 cc; range 90-160 cc). According to the data obtained by tonometry, a statistically significant difference was found between the average pre-filling and post-filling pressures of group A (28.4 and 66.5 mmHg, respectively) and group B (22.1 and 64.3 mmHg, respectively). Clinical benefits of pre-filling topical applications of 60% DMSO observed in our trial were an enhancement of the total volume inflatable per session and a significant shortening of the total expansion period.

Intercellular adhesion molecule-1 (ICAM-1) and granulocyte-macrophage colony stimulating factor (GM-CSF) co-expression in cutaneous malignant melanoma lesions.

The expression of intercellular adhesion molecule-1 (ICAM-1) and granulocyte-macrophage colony stimulating factor (GM-CSF) was investigated in 25 melanoma patients by evaluating 34 fresh biopsy specimens. ICAM-1 in situ hybridization and immunochemistry for ICAM-1 and GM-CSF were performed. Most of the metastatic melanoma samples (12 out of 18) and a few of the primary melanoma lesions (three out of 16) showed ICAM-1 expression. The expression of ICAM-1 was significantly (P < 0.01) higher in metastatic lesions than in primary tumours. GM-CSF mRNA and protein were detected in 10 of the 18 metastatic samples and in two of the 15 primary lesions. A significantly high degree (P < 0.0002) of concordance between ICAM-1 and GM-CSF expression was observed: the samples that were negative or positive for ICAM-1 expression were correspondingly negative or positive for GM-CSF. Correlation with clinical and histological parameters was examined. The expression of both molecules in metastatic samples was found to be significantly (P < 0.001) associated with a shorter recurrence-free period. These findings, if confirmed by a wider number of patients, could suggest the prognostic value of the simultaneous, and probably co-ordinated, expression of ICAM-1 and GM-CSF. They also highlight the importance of preventive molecular and biochemical characterization of neoplastic cell cytokine receptors, specifically focusing on the particular cytokine to be used as anticancer therapy and/or as adjunct to chemotherapy.