Cellular fibronectin mediates the adhesion of cells with the extracellular matrix and thus probably regulates tumor invasion. Evaluation of proliferating cell nuclear antigen expression and counting of silver nuclear organizer regions potentially assess proliferative fraction and biologic aggressiveness in several malignancies. We investigated the above markers’ prognostic value in 60 malignant melanomas of the skin. Deep Clark levels were statistically associated with discontinuous fibronectin staining pattern (SPII) (P < .05) as well as with high proliferating cell nuclear antigen and silver nuclear organizer regions indexes (P < .01 and P < .05, respectively). Fibronectin staining pattern (SPII) was frequently observed in thick melanomas (P < .05). High proliferating cell nuclear antigen immunoreactivity positively correlated with mitotic activity (P < .05), the presence of vertical growth phase (P < .05), and increased silver nuclear organizer regions counts (P < .05). Patients with continuous fibronectin staining pattern (SPI) and low proliferating cell nuclear antigen scores were unlikely to develop metastatic disease (P < .01). Therefore, the simultaneous comparative assessment of these factors is very promising in predicting melanomas clinical evolution.
MakaremRNewhamPAskariJAGreenJLClementsJEdwardsMHumphriesMJMouldAP.Competitive binding of vascular cell adhesion molecule-1 and the HepII/IIICS domain of fibronectin to the integrin alpha 4 beta 1. J Biol Chem11:269:4005–4011, 1994.
2.
NataliPGNicotraMRBartolazziACavaliereRBigottiA.Integrin expression in cutaneous malignant melanoma: Association of the alpha 3/beta 1 heterodimer with tumor progression. Int J Cancer54:68–72, 1993.
3.
LauriDDe GiovanniCBiondelliTLalliELanduzziLFacchiniANicolettiGNanniPDejanaELolliniP-L.Decreased adhesion to endothelial cells and matrix proteins of H-2Kb gene transferred tumour cells. Br J Cancer68:862–867, 1993.
4.
RungerTMKleinCEBeckerJCBrockerE-B.The role of genetic instability, adhesion, cell motility and immune escape mechanisms in melanoma progression. Cur Opin Oncol6:188–196, 1994.
5.
MartinGRRohrbachDHTerranovaVPLiottaLA.Structure, function and pathology of basement membranes. In WagnerBFleischmayerRKaufmanN (eds). Connective tissue diseases. International Academy of Pathology Monograph. Williams & Wilkins, Baltimore, pp. 16–25, 1983.
6.
AkiyamaSKYamadaKM.Fibronectin in disease. In WagnerBFleischmayerRKaufmanN (eds). Connective tissue diseases. International Academy of Pathology Monograph. Williams & Wilkins, Baltimore, pp. 55–96, 1983.
7.
UrsoCBondiRBalziMSculbaEMauriPBeccioliniATarocchiSVallecchiC.Cell kinetics of melanocytes in common and dysplastic nevi and in primary and metastatic cutaneous melanoma. Pathol Res Pract188:323–329, 1992.
8.
HallPALevinsonDA.Assessment of cell proliferation in histological material. J Clin Pathol43:184–192, 1990.
9.
RummeltVGardnerLMFolbergRBeckSKnospBMoningerTOMooreKC.Three-dimensional relationships between tumor cells and microcirculation with double cyanine immunolabeling, laser scanning confocal microscopy, and computer-assisted reconstruction: An alternative to case corrosion preparations. J Histochem Cytochem42:681–686, 1994.
10.
FairmanMP.DNA polymerase-δ/PCNA: Actions and interactions. J Cell Sci94:1–4, 1990.
11.
TokudaYMukaiKMatsunoYFuruyaSShimosatoYTakasakiYSaidaTIshiharaK.Proliferative activity of cutaneous melanocytic neoplasms defined by a proliferating cell nuclear antigen labelling index. Arch Dermatol Res284:319–323, 1992.
12.
GambiniCCasazzaSBorgianiLCanepaMRovidaSRongiolettiFReboraA.Counting the nucleolar organizer region-associated proteins is a prognostic clue of malignant melanoma. Arch Dermatol128:487–490, 1992.
13.
CentenoBALouisDNKupskyWJPrefferFISobelRA.The AgNOR technique, PCNA immunohistochemistry, and DNA ploidy in the evaluation of choroid plexus biopsy specimens. Anat Pathol690–696, 1993.
14.
McGovernVJ.The classification of malignant melanoma and its histological repeating. Cancer32:1446–1457, 1973.
15.
ClarkWHJr.A classification of malignant melanoma in man correlated with histogenesis and biologic behavior. In Advances in biology of the skin. Vol. III, Pergamon Press, New York, pp. 621–647, 1967.
16.
BreslowA.Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Am Surg172:902–908, 1970.
17.
ElderDEMurphyGF (eds). Melanocytic tumors of the skin. Atlas of tumor pathology, AFIP, Bethesda, MD, 1991.
18.
CooperRWaneboHHagarW.Regression in thin malignant melanoma. Arch Dermatol121:1985.
19.
ElderDE.Prognostic guides to melanomas. In MackieRM (Ed). Clinics in oncology. WB Saunders, London, pp. 457–475, 1984.
CrockerJBoldyDAREganMJ.How should we count AgNORs? Proposals for a standardized approach. J Pathol158:185–188, 1989.
22.
CrockerJ.Nucleolar organiser regions. Curr Top Pathol82:91–149, 1990.
23.
DanenEHJVan MuijenGNPVan De Wiel-Van KemenadeEJansenKFJRuiterDJFigdorCG.Regulation of integrin-mediated adhesion to laminin and collagen in human melanocytes and in non-metastatic and highly metastatic human melanoma cells. Int J Cancer54:315–321, 1993.
24.
SaikiI.Inhibition of tumor cell adhesion and metastasis. Gan To Kagaku Ryoho20:363–372, 1993.
MorelliJGYohnJJZekmanTNorrisDA.Melanocyte movement in vitro: Role of matrix proteins and integrin receptors. J Invest Dermatol101:605–608, 1993.
27.
SeftorRESeftorEAStetler-StevensonWGHendrixMJ.The 72 KDa type IV collagenase is modulated via differential expression of alpha v beta 3 and alpha 5 beta 1 integrins during human melanoma cell invasion. Cancer Res53:3411–3415, 1993.
28.
MaedaTOyamaRTitaniKSekiguchiK.Engineering of artificial cell adhesive proteins by grafting EILDVPST sequence derived from fibronectin. J Biochem113:29–35, 1993.
29.
WojtukiewiczMZTangDGCiarelliJJNelsonKKWalzDADiglioCAMammenEFHonnKV.Thrombin increases the metastatic potential of tumor cells. Int J Cancer54:793–806, 1993.
30.
HataiMHashiHKatoIYaoiY.Inhibition of cell adhesion by proteolytic fragments of type V collagen. Cell Struct Funct18:53–60, 1993.
31.
HardanIWeissLHershkovizRGreenspoonNAlonRCahalonLReichSSlavinSLiderO.Inhibition of metastatic cell colonization in murine lungs and tumor-induced morbidity by non-peptidic Arg-Gly-Asp mimetics. Int J Cancer55:1023–1028, 1993.
32.
KomazawaHSaikiIAokiMKitaguchiHSatohHKojimaMOnoMItohIAzumaI.Synthetic Arg-Gly-Asp-Ser analogues of the cell recognition site of fibronectin that retain antimetastatic and anti-cell adhesive properties. Biol Pharm Bull16:997–1003, 1993.
33.
SipesJMGuoNNegreEVogelTKrutzschHCRobertsDD.Inhibition of fibronectin binding and fibronectin-mediated cell adhesion to collagen by a peptide from the second type 1 repeat of thrombospondin. J Cell Biol121:469–477, 1993.
34.
SituRInmanDRFligielSEVaraniJ.Effects of all-trans-retinoic acid on melanocyte adhesion and motility. Dermatology186:38–44, 1993.
35.
KawanoTTakasakiSTaoTWKobataA.Altered glycosylation of beta 1 integrins associated with reduced adhesiveness to fibronectin and laminin. Int J Cancer53:91–96, 1993.
36.
SaikiIYonedaJKobayashiHIgarashiYKomazawaHIshizakiYKatoIAzumaI.Antimetastatic effect by anti-adhesion therapy with cell-adhesive peptide of fibronectin in combination with anticancer drugs. Jpn J Cancer Res84:326–335, 1993.
37.
RepeshLADrakeSRWarnerMCDowningSWJyringRSeftorEAHendrixMJMcCarthyJB.Adriamycin-induced inhibition of melanoma cell invasion is correlated with decreases in tumor cell motility and increases in focal contact formation. Clin Exp Metastasis11:91–102, 1993.
38.
KuwataTKitagawaMKasugaT.Proliferative activity of primary cutaneous melanocytic tumours. Virch Archiv A Pathol Anat423:359–364, 1993.
39.
TakahashiHStruttonGMParsonsPG.Determination of proliferating fractions in malignant melanomas by anti-PCNA/cyclin monoclonal antibody. Histopathol18:221–227, 1991.
40.
TuPMiyauchiSMikiY.Proliferative activities in Spitz nevus compared with melanocytic nevus and malignant melanoma using expression of PCNA/cyclin and mitotic rate. Am J Dermatopathol15:311–314, 1993.
41.
RiegerEHofmann-WellenhofRSoyerHPKoflerRCerroniLSmolleJKerlH.Comparison of proliferative activity as assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 monoclonal antibodies in melanocytic skin lesions. A quantitative immunohistochemical study. J Cutan Pathol20:229–236, 1993.
42.
EvansATBlesingKOrrellJMGranA.Mitotic indices, anti-PCNA immunostaining and AgNORs in thick cutaneous melanomas displaying paradoxical behaviour. J Pathol168:15–22, 1992.
43.
PelosiGZamboniGDoglioniCRodellaSBresaolaEIaconoCSerioGIannucciAScarpaA.Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignancy in endocrine tumors of the pancreas. Am J Surg Pathol16:1215–1225, 1992.
44.
LuCKerbelRS.Cytokines, growth factors and the loss of negative growth controls in the progression of human cutaneous malignant melanoma. Cur Opin Oncol6:212–220, 1994.
45.
ClarkWHJrElderDEGuerryDEpsteinMNGreenMHHornMV.A study of tumor progression. Hum Pathol15:1147–1165, 1984.
46.
TrereD.Technical and methodological aspects of silver staining and measurement of nucleolar organizer region (NOR). Zentralbl Pathol149:11–14, 1994.
47.
HeinischGBarthJ.Use of the AgNOR method for the differential diagnosis of tumors and for the quantification of nonneoplastic epidermal hyperproliferation in dermatohistology. Zentralbl Pathol140:95–101, 1994.
48.
CarrilloRSneigeNEl NaggarAKInterphase nucleolar organizer regions in the evaluation of serosal cavity effusions. Acta Cytol38:367–372, 1994.
49.
ReboraA.Prognosing melanomas: The argyrophilic nucleolar organizer region approach. Dermatol185:166–168, 1992.
