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PubMed2004

Genetic evolution in colon cancer KM12 cells and metastatic derivates.

So far, CRC cell lines have contributed to descriptions of 2 patterns of genetic instability, affecting either microsatellite sequences or chromosome number and structure. Often, these patterns are mutually exclusive; while near-diploid karyotypes usually appear with MSI and chromosomal stability, near-triploid or tetraploid cells display a high degree of CIN and are stable at the microsatellite level. In the present study, we describe the genomic instability pattern of KM12 CRC cells. KM12C and derived cell lines with different metastatic properties were analyzed by conventional cytogenetics, CGH and M-FISH. Results were compared to 5 cell lines usually used as model of MSI and CIN. Concordance between our results and previously published SKY data are also reviewed. Interestingly, the poorly metastatic KM12C cell line displayed a near-diploid karyotype with high levels of structural chromosome instability and microsatellite instability. The highly metastatic KM12SM and KM12L4A cell lines showed polyploid karyotypes and maintained CIN and MSI. A comparison between karyotypes of poorly and highly metastatic KM12 cell lines allowed us to delineate a cytogenetic evolution pathway. Our results clearly demonstrated that endoreduplication was the origin of the polyploid dosages in the highly metastatic forms following the monosomic model postulated for CRC. Therefore, we demonstrate that KM12C cells and their metastatic derivates, KM12SM and KM12L4A, are a useful model of chromosomal evolution where MSI may coexist with CIN.

Cell Line, Tumor↗

PubMed2005

HPA binding and metastasis formation of human breast cancer cell lines transplanted into severe combined immunodeficient (scid) mice.

Six human breast cancer cell lines were injected subcutaneously into scid mice and their in vivo growth behaviour and HPA binding pattern were analysed. Furthermore, the role of HPA binding glycoconjugates concerning the adhesion to endothelial cells in vitro was investigated. Four of the tested cell lines engrafted in the scid mouse model but they showed considerable variations concerning their growth behaviour, their metastatic potential and their HPA binding pattern. HPA inhibited adhesive interactions between cell lines derived from metatstatic sources and tumour necrosis factor (TNF)alpha stimulated endothelial cells. The transplantation of HPA defined breast cancer cell lines into scid mice is a useful animal model for the research of breast cancer and its metastasis. The HPA binding glycoconjugates appear to be associated with adhesive interactions between metastasising tumour cells and endothelial cells.

Acetylgalactosamine↗

PubMed2002

Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary.

The expressions of cytokeratin (CK) 7 and 20 have been studied in various primary and metastatic carcinomas, and their determination may help distinguish the site of origin of metastatic carcinomas. However, little is known about the factors that determine variations in their expression patterns in primary gastric and colorectal carcinomas. We investigated the expressions of CK7 and CK20 in 289 cases of gastric carcinoma and 225 cases of colorectal carcinoma using a tissue microarray. To evaluate CK7 and CK20 expression patterns of ovarian metastases from gastric or colorectal carcinomas, 54 cases of metastatic carcinomas to the ovary were examined. It was found that 71% (207 of 289) of the gastric carcinomas stained positively for CK7, whereas only 9% (21 of 225) of the colorectal carcinomas proved to be CK7 positive, and that 41% (117 of 289) of the gastric carcinomas and 73% (165 of 225) of the colorectal carcinomas were CK20 positive. The proportion of CK7+/CK20- was highest in the gastric carcinomas at 46% (132 of 289), and was independent of the histologic classification of Lauren (46% of the intestinal type, 45% of the diffuse type). The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histologic grade and location of the tumor. CK7-/CK20+ had the greatest proportion (68%) in colorectal carcinomas, and this was dependent on the tumor's histologic grade (75% of low-grade versus 52% of high-grade) and location (46% of right-sided versus 76% of left-sided). Moreover, 42% (18 of 43) of gastric carcinomas metastatic to the ovary were CK7+/CK20-, whereas 19% (8 of 43) were CK7-/CK20+. All colorectal cancers metastatic to the ovary were CK7-/CK20+, except 1 case that was CK7-/CK20-. In conclusion, the CK7 and CK20 expression patterns in primary gastric carcinomas vary considerably, and those in colorectal carcinomas are associated with histologic grade and tumor location. The CK7-/CK20+ expression pattern is specific for metastatic colorectal carcinomas to the ovary, but has low predictability for colorectal origin in metastatic ovarian carcinoma.

Adenocarcinoma↗

PubMed1989

Characterization of a metastasis-deficient lectin-resistant human melanoma mutant.

A mutant (3S5), almost completely deficient in pulmonary metastatic ability in nude mice, was recently isolated from a human malignant melanoma cell line (MeWo). The WGA-resistance (WGAr) phenotype of 3S5 cells was accompanied by a collateral hypersensitivity to the lectin BSII (Bandeiraea simplicifolia), similar to that observed previously in class-I non-metastatic WGAr recessive genetic mutants isolated from a highly metastatic mouse tumor. The lectin-resistance/sensitivity profile of 3S5 cells was completely stable in tissue culture for 9 months when the cells were grown in the absence of WGA. Twenty independent clones of 3S5 were analyzed and all manifested a similar lectin-resistance pattern, and severe deficiency in pulmonary metastatic ability following i.v. or s.c. inoculation, when compared to the parent MeWo cells. Some heterogeneity in metastasis was noted, especially with respect to occasional extrapulmonary spread. The majority of the small number of metastases obtained after i.v. inoculation of 3S5 cells maintained the lectin-resistance profile and deficient metastatic potential characteristic of 3S5 cells upon re-inoculation into other nude mice. The results provide further evidence that cell-surface glycosylation changes can significantly after metastatic potential, including that of human tumors.

Aged↗

PubMed2004

Primary vulvar melanoma with satellite metastasis: dermoscopic findings.

A 79-year-old woman presented with a 1-year history of a pigmented nodular lesion on the left labium minor. Histopathology of the nodule led to a diagnosis of metastatic melanoma. A pigmented flat lesion on the inner side of the left labium major was also biopsied and was found to be a superficial spreading melanoma. The dermoscopic findings of primary and metastatic vulvar melanoma which simultaneously occurred in the same patient are described. Dermoscopy revealed a homogeneous pattern associated with linear irregular vessels in the metastatic nodule, while irregular globules and streaks were seen in the primary melanoma.

Aged↗

PubMed1994

DNA stemline heterogeneity of non-small cell lung carcinomas and differences in DNA ploidy between carcinomas and metastatic nodes.

Nuclear DNA contents were measured using a flow cytometry technique in non-small cell lung carcinomas and differences in ploidy patterns were compared between primary lung carcinomas and metastatic lymph nodes. Negative node lung cancer revealed diploidy in 82.6% of the 224 non-small cell lung cancers, in contrast with 19.5% in positive node lung cancer. In multi-stemline cells, a high incidence of nodal involvement was seen when compared with single stemline cells. The more the DNA indices increased, the more the lymph nodes were seen to be extensively involved. Furthermore, intratumoral heterogeneity was evaluated in terms of n-categories. In conclusion, it is suggested that nodal metastasis may be caused by tumor cells with high DNA indices in lung carcinomas, in particular for multi-stemline cells.

Adenocarcinoma↗

PubMed1997

Correlation of metastasis-related gene expression with metastatic potential in human prostate carcinoma cells implanted in nude mice using an in situ messenger RNA hybridization technique.

The purpose of this study was to determine whether the expression level of several metastasis-regulating genes correlates with the metastatic potential of human prostate cancer cells implanted into the prostate of nude mice. The steady-state mRNA expression levels for epidermal growth factor receptor (EGFR; growth), basic fibroblast growth factor (bFGF) and interleukin (IL)-8 (angiogenesis), 72-kd and 92-kd type IV collagenase (invasion), E-cadherin (adhesion), and multidrug resistance (mdr-1; drug resistance) were measured by Northern blot and colorimetric in situ hybridization techniques in human PC-3M cells and selected cell variants with different metastatic potentials. Highly metastatic cells growing in culture constitutively and uniformly expressed higher levels of bFGF, IL-8, type IV collagenase, and mdr-1 mRNA transcripts than parental PC-3M cells or low metastatic cells, which displayed a heterogeneous pattern of gene expression. Human prostate cancer cells implanted in nude mice at an ectopic site (subcutaneous) expressed lower levels of EGFR, mdr-1, bFGF, IL-8, and collagenase type IV than those implanted in an orthotopic site (prostate), indicating that the expression of these genes was dependent on the organ environment. Highly metastatic cells growing in the prostate expressed higher levels of EGFR, bFGF, type IV collagenase, and mdr-1 mRNA than low metastatic parental cells in the same site. These data demonstrate a direct correlation between the expression of several metastasis-related genes and the metastatic potential of human prostate cancer cells in nude mice and suggest that multiparametric in situ hybridization analyses can be used to identify the metastatic potential of individual patients' prostate cancers.

Animals↗

PubMed1984

Cathepsin B-like proteinase as a marker for metastatic tumor cell variants.

Serial transplantation of a spontaneous BDX rat tumor, classified as an anaplastic sarcoma, gives rise to two variants; a rapidly growing nonmetastatic line (AS) and a slowly growing, invasive, and highly metastatic variant (ASML). The availability of two cell lines of the same origin but with markedly differing metastatic potential offers an ideal model for the identification of the cellular properties involved in invasive and/or metastatic behavior. The present work focuses on the pattern of various proteinases in the two tumor cell variants. The findings disclosed one major consistent difference which relates to a cathepsin B-like cysteine proteinase. The metastatic ASML variant manifests exceedingly high intracellular cathepsin B-like activity; in the nonmetastatic AS variant, the activity of this proteinase is significantly lower. Other proteinases, in particular elastase-like, chymotrypsin-like, collagenase-like enzymes and plasminogen activator, showed low, essentially comparable activity patterns. Thus, cathepsin B-like proteinase is a marker enzyme of the metastatic ASML tumor cell variant.

Animals↗

PubMed2001

Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to screen for changes in the number of DNA sequence copies in 30 primary colorectal cancers and 16 liver metastases, to identify regions that contain genes important for the development and progression of colorectal cancer. In primary colorectal cancer, we found frequent gains at 7p21 (36.7%), 7q31-36 (30%), 8q23-24 (43.0%), 12p (30%), 14q24-32 (33.3%), 16p (40.0%), 20p (33.3%), 20q (63.3%) and 21q (36.3%), while loss was often noted at 18q12-23 (36.7%). In metastatic tumors, there were significantly more gains and losses of DNA sequences than in primary tumors, with gains at 8q23-24 (found in 62.5% of recurrences vs. 43.0% of primary tumors), 15q21-26 (37.5% vs. 20.0%), 19p (43.8% vs. 20.0%) and 20q (81.3% vs. 63.3%) and losses at 18q12-23 (50.0% vs. 36.7%). The pattern of genetic changes seen in metastatic tumors, with frequent gains at 8q23-24 and 20q and loss at 18q12-23, suggests the progression of colorectal cancer. We investigated a clinical follow-up study for all patients examined by CGH and directed our attention to the genetic changes consisting of gains at 8q and 20q. The incidence of liver metastases was higher in patients with primary colorectal cancer with these genetic changes. Gains at 8q and 20q might be useful to identify patients at high risk for developing liver metastases.

Chromosome Aberrations↗

PubMedDate not supplied

Cystic changes in intraabdominal extrahepatic metastases from gastrointestinal stromal tumors treated with imatinib.

OBJECTIVE: This study was undertaken for the purpose of describing the CT features of intra-abdominal extra-hepatic metastases from gastrointestinal stromal tumors in patients who were treated with imatinib. MATERIALS AND METHODS: Eleven patients with intra-abdominal extra-hepatic metastases from gastrointestinal stromal tumors, who were treated with imatinib between May 2001 and December 2003, were included in this study. The clinical findings and CT scans were retrospectively reviewed. The metastatic lesions were assessed according to the location, size (greatest diameter), attenuation, and the enhancing pattern before and after imatinib treatment. RESULTS: Prior to the treatment, the sizes and attenuation values of the metastatic lesions ranged from 5 to 20 cm and from 63 to 131 H, respectively. The metastatic lesions showed a heterogeneous enhancement pattern on the contrast-enhanced CT scans. After the treatment, the metastatic lesions became smaller in all 11 patients, and the corresponding attenuation value ranged from 15 to 51 H. The metastatic lesions became homogeneous and cystic in appearance on the follow-up CT scans, mimicking ascites. CONCLUSION: Intra-abdominal extra-hepatic metastases of patients with gastrointestinal stromal tumors treated with imatinib may appear as well-circumscribed cystic lesions on contrast-enhanced CT. These metastases are likely to become smaller and resemble ascites, but may persist indefinitely on the followup CT.

Adult↗

PubMed1988

Histopathology of canine bone marrow in malignant lymphoproliferative disorders.

Bone marrow core biopsies from 63 dogs with malignant lymphoproliferative disorders and leukemic involvement were evaluated. Multicentric lymphoma (44), multiple myeloma (8), chronic lymphocytic leukemia (9), and acute lymphoblastic leukemia (2) were found. Four distinct bone marrow histologic patterns were identified: focal (6), mixed (20), interstitial (28), and packed (9). Of those with focal or mixed patterns, 77% (20/26) had paratrabecular distribution. Stromal changes were infrequent, with 6% (4/63) having necrosis, 3% (2/63) fibrosis, and 6% (4/63) osteolysis. For each condition, the interstitial and mixed patterns were the most common presentations, while focal and packed patterns occurred less frequently. Morphologically, cells of metastatic lesions of lymphoma resembled those of primary sites. Colonization of bone marrow by various cytologic types of lymphoma was independent of the histologic patterns.

Animals↗

PubMed1996

Patterns-of-failure analysis of patients with high pretreatment prostate-specific antigen levels treated by radiation therapy: the need for improved systemic and locoregional treatment.

PURPOSE: The patterns of failure (local and/or regional v metastatic) have been determined for patients with prostate cancer and pretreatment prostate-specific antigen (PSA) levels > or = 20 ng/mL treated with radiation alone with the purpose to design appropriate multimodal treatments. MATERIALS AND METHODS: One hundred twenty patients with pretreatment PSA levels > or = 20 ng/mL were treated with external-beam radiation alone between February 1988 and October 1993. They were arbitrarily divided by PSA levels, 20 to 29.9 ng/mL, 30 to 49.9 ng/mL, and > or = 50 ng/mL, and analyzed in terms of freedom from any failure (no evidence of biochemical disease [bNED], and PSA level < 1.5 ngm/mL and not increasing), as well as freedom from imaging evidence of distant metastasis (fdm). RESULTS: There was no significant difference in short-term outcome by pretreatment PSA level, and thus all patients were pooled for analysis. At 4 years, 81% were fdm and 28% were free of any failure. This suggests that approximately 50% have recurred with local and/or regional disease or undetectable metastatic disease. Multivariate analysis indicated that low palpation stage and higher center of prostate dose were associated with better bNED survival. Multivariate analysis indicated that increasing stage and younger age are significantly associated with increasing distant metastasis. CONCLUSION: Patients with pretreatment PSA levels > or = 20 ng/mL are not optimally treated by irradiation alone. The pattern of failure suggests improvement may come from systemic treatment of metastatic disease and high-dose radiation to improve locoregional disease. To evaluate this, we have begun a multimodal trial of chemohormonal therapy followed by extended-field irradiation.

Analysis of Variance↗

PubMed1999

Differential diagnosis of cervical lymph nodes in head and neck cancer by ultrasonography.

OBJECTIVE: Determination of whether an enlarged cervical lymph node is metastatic or not is clinically important in head and neck oncology. Differential diagnosis of the lymph node, however, is still a diagnostic problem. The purpose of this study is to clarify the ultrasonographic findings of the metastatic lymph nodes of head and neck squamous cell carcinoma and to establish the criteria. METHODS: We investigated 36 metastatic lymph nodes in head and neck squamous cell carcinoma and 24 non-metastatic nodes in benign disease with a 10-MHz transducer. We examined the size, shape, and internal echo (echo level, punctate bright echogenic spots, hilus echogenic line, cystic pattern) of these nodes. Based on this investigation, we evaluated 70 lymph nodes from 25 other patients by ultrasonography. RESULTS: The short axis diameter and shape of metastatic nodes were larger and rounder than those of non-metastatic ones. Of the metastatic nodes, 69% showed hypoechoic and 31% isoechoic levels, and 78% exhibited punctate bright echogenic spots. Of the non-metastatic nodes, 92% showed hypoechoic and 8% isoechoic levels, and none of them showed the spots. The hilus echogenic line was not present in any metastatic node, but it was seen in 58% of non-metastatic ones. Of the metastatic nodes, 19% exhibited a cystic pattern; none of the non-metastatic nodes showed the pattern. According to our criteria based on these results, the accuracy rate was 98.6% (69/70). The sensitivity and specificity were 97.2% (35/36) and 100% (34/34), respectively. The false positive rate and the false negative rate were 0% (0/70) and 1.4% (1/70), respectively. CONCLUSION: Internal echo findings and shape of lymph nodes can be an important diagnostic tool, and our ultrasonographical criteria of the lymph nodes are very useful for the differential diagnosis of the cervical lymph nodes.

Biopsy↗

PubMed2001

Chromosomal imbalances in primary and metastatic melanomas revealed by comparative genomic hybridization.

Characteristic genetic changes underlying the metastatic progression of malignant melanoma is incompletely understood. The goal of our study was to explore specific chromosomal alterations associated with the aggressive behavior of this neoplasm. Comparative genomic hybridization was performed to screen and compare genomic imbalances present in primary and metastatic melanomas. Sixteen primary and 12 metastatic specimens were analyzed. We found that the pattern of chromosomal aberrations is similar in the two subgroups; however, alterations present only in primary and/or metastatic tumors were also discovered. The mean number of genetic changes was 6.3 (range 1-14) in primary and 7.8 (range 1-16) in metastatic lesions. Frequent losses involved 9p and 10q, whereas gains most often occurred at 1q, 6p, 7q, and 8q. Distinct, high-level amplifications were mapped to 1p12-p21 and 1p22-p31 in both tumor types. Amplification of 4q12-q13.1, 7q21.3-qter and 8q23-qter were detected only in primary tumors. The 20q13-qter amplicon was present in a metastatic tumor. The number of genetic alterations were significantly higher in primary tumors which developed metastases within one year after the surgery compared to tumors without metastasis during this time period. Fluorescence in situ hybridization with centromeric and locus-specific probes was applied to validate CGH results on a subset of tumors. Comparison of FISH and CGH data gave good correlation. The aggressive behavior of melanoma is associated with accumulation of multiple genetic alterations. Chromosome regions, which differ in the primary and metastatic lesions, may represent potential targets to identify metastases-related chromosomal alterations.

Adult↗

PubMed2001

Metastatic metanephric adenoma with foci of papillary carcinoma in a child: a combined histologic, immunohistochemical, and FISH study.

We report an example of metastatic metanephric adenoma containing foci of papillary carcinoma in the primitive tumor arising in the left kidney of an 11-year-old girl. Histology revealed a monomorphous population of small cells with bland cytology arranged in pseudoglandular, tubular, papillary, and glomeruloid structures with frequent psammoma bodies. Intermixed there were foci of and small cavities lined by larger cells with eosinophilic cytoplasm and larger nuclei with small nucleoli. A regional lymph node contained metastatic deposits with the former histologic pattern. By immunohistochemistry the small cells were negative for carcinoembryonic antigen (CEA) and keratin 7 while these antibodies reacted positively in the larger cells. A fluorescent in-situ hybridization (FISH) study for chromosome 17 in imprints from the primitive tumor revealed 3 signals in about 10% of the nuclei while the rest was disomic. Disaggregated cells from the metastatic lymph node consistently revealed 2 signals for chromosomes 7, 16, and l7. Histology of the primitive tumor resembled the epithelial component of the so-called metanephric adenofibroma while the metastatic lymph node exhibited histologic and FISH genomic features of metanephic adenoma. Int J Surg Pathol 9(3):241-247, 2001

Adenofibroma↗

PubMed1989

Blood group-related antigens in human kidney: modulation of Lewis determinants in renal cell carcinoma.

Seven mouse monoclonal antibodies and the lectin Ulex europaeus, detecting blood group related antigens of the ABH and Lewis systems, have been used to determine the immunophenotype of human renal cell carcinomas. Immunohistochemical analyses have demonstrated that these antigenic systems are differentially expressed by distinct normal cell types and domains of the human nephron. In the present study we analyzed the immunophenotype of 29 primary and 15 metastatic renal carcinomas by the immunoperoxidase method. Blood type was known in all of the cases and secretor status in nine cases. ABH specificities were not detected in tumor cells of the primary tumors studied, although two of the metastases showed heterogeneous expression of H and A antigens, respectively. Lewisx (Lex) determinant was detected in 76% of primary renal cell carcinomas; however, Lex was only expressed by occasional cells in 20% of the metastatic tumors analyzed. Lewisa (Lea) was detected with a heterogeneous pattern of expression in 31% of the primary and 26% of the metastatic renal tumors studied. Lewisy (Ley) antigen expression was found in 17% of the primary and 20% of the metastatic tumors analyzed. Detection of precursor type 1 structure was observed in 28% of primary and 20% of metastatic renal cell carcinomas. The present study suggests the histogenesis of renal cell carcinoma in the proximal nephron, based on the expression of Lex and Lea antigens. It also shows: (a) an apparent deletion, downregulation or structural modification of Lex determinant in most of the metastatic tumors; (b) undetectable levels of ABH specificities in tumor cells of primary renal cell carcinoma; and (c) enhanced expression and/or neosynthesis of precursor type 1 structure and Ley determinant in some renal cell carcinomas.

ABO Blood-Group System↗

PubMed2004

Accuracy of the determination of S100B protein expression in malignant melanoma using polyclonal or monoclonal antibodies.

AIMS: To compare the routinely used polyclonal anti-S100 and a mouse monoclonal anti-S100B antibody for their accuracy in the detection of the S100B expression profile (pattern and intensity) in a series of 67 primary (n = 37) and lymph node metastatic (n = 30) melanoma tissues. S100B is the lineage marker of malignant melanoma. Antibodies routinely used for melanoma diagnosis are not necessarily specific for this protein. Furthermore, clinical monitoring of melanoma progression is mostly based on the determination of serum S100B protein levels without knowing the actual expression level in the primary and/or metastatic tissue. METHODS AND RESULTS: The profile of expression patterns (focal, heterogenous and diffuse) as well as intensity ranges (+, ++ and +++) were similar for the two antibodies in melanoma tissues. However, comparison of the patterns and intensities on the basis of individual cases revealed a high frequency of discrepancies (50.7 and 58.2%, respectively). Severe discrepancy between the two antibodies in the determination of the S100B protein expression pattern (focal versus diffuse or focal versus heterogeneous) was relatively frequent; 13.4 and 11.9%, respectively. Furthermore, a similar rate of severe discrepancy was observed between the two antibodies in the determination of the intensity of S100B expression levels (+ versus +++ or + versus ++); 19.4 and 8.9%, respectively. Separate analysis of the primary tumours and metastases gave similar results. CONCLUSION: For the accurate determination of S100B protein expression in malignant melanoma it is highly recommended that a monospecific antibody is used.

Adult↗

PubMedDate not supplied

The relevance of adhesion molecules in the classification of squamous cell carcinoma of the head and neck.

BACKGROUND: Clinical studies have demonstrated increased serum levels of E-selectin, P-selectin and VCAM-1 in patients with squamous cell carcinomas, which correlate with expression in the primary tumour. For this reason, selectin expression may also support the diagnosis and be of prognostic value in squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Using immunohistochemistry, the expressions of E- and P-selectin and VCAM-1 in SCCHN were characterised and analysed. RESULTS: The expressions of E-selectin and VCAM-1 were increased. The magnitude of expression was unrelated to the location or size of the primary tumour. With increasing de-differentiation, the expression of E-selectin increased, whereas the number of cells expressing VCAM-1 was highly variable. In contrast, E-selectin and VCAM-1 expressions decreased with progressive metastatic disease. CONCLUSIONS: These data demonstrate that the expression patterns of E-selectin and VCAM-1 may depend on differentiation and lymphogenic metastatic disease in SCCHN, and suggest that these molecules may have a dual role, depending on the stage of tumour development. These findings support the hypothesis that expression of E-selectin and VCAM-1 may be initiated by the release of tumour necrosis factor-alpha (TNF-alpha) at an early stage of tumour development. In contrast, the decrease in selectin expression, observed as the metastatic disease progresses, may serve as a protective mechanism to prevent an influx of effector cells.

Carcinoma, Squamous Cell↗