Risk stratification in GIST: shape quantification with CT is a predictive factor.

BACKGROUND: Tumor shape is strongly associated with some tumor's genomic subtypes and patient outcomes. Our purpose is to find the relationship between risk stratification and the shape of GISTs. METHODS: A total of 101 patients with primary GISTs were confirmed by pathology and immunohistochemistry and underwent enhanced CT examination. All lesions' pathologic sizes were 1 to 10 cm. Points A and B were the extremities of the longest diameter (LD) of the tumor and points C and D the extremities of the small axis, which was the longest diameter perpendicular to AB. The four angles of the quadrangle ABCD were measured and each angle named by its summit (A, B, C, D). For regular lesions, we took angles A and B as big angle (BiA) and small angle (SmA). For irregular lesions, we compared A/B ratio and D/C ratio and selected the larger ratio for analysis. The chi-square test, t test, ROC analysis, and hierarchical or binary logistic regression analysis were used to analyze the data. RESULTS: The BiA/SmA ratio was an independent predictor for risk level of GISTs (p = 0.019). With threshold of BiA at 90.5°, BiA/SmA ratio at 1.35 and LD at 6.15 cm, the sensitivities for high-risk GISTs were 82.4%, 85.3%, and 83.8%, respectively; the specificities were 87.1%, 71%, and 77.4%, respectively; and the AUCs were 0.852, 0.818, and 0.844, respectively. LD could not effectively distinguish between intermediate-risk and high-risk GISTs, but BiA could (p < 0.05). Shape and Ki-67 were independent predictors of the mitotic value (p = 0.036 and p < 0.001, respectively), and the accuracy was 87.8%. CONCLUSIONS: Quantifying tumor shape has better predictive efficacy than LD in predicting the risk level and mitotic value of GISTs, especially for high-risk grading and mitotic value > 5/50HPF. KEY POINTS: • The BiA/SmA ratio was an independent predictor affecting the risk level of GISTs. LD could not effectively distinguish between intermediate-risk and high-risk GISTs, but BiA could. • Shape and Ki-67 were independent predictors of the mitotic value. • The method for quantifying the tumor shape has better predictive efficacy than LD in predicting the risk level and mitotic value of GISTs.

Malignant jejunal gastrointestinal stromal tumor with history of prostate cancer: A case report.

RATIONALE: The problem of the coexistence of gastrointestinal stromal tumor (GIST) with other neoplasms is complex, and carcinomas of prostate is one of the common types of GIST-associated cancers. Doubling time of GIST is about 3.9 months for high-risk GIST, and the treatment paradigm for GIST has required the integration of surgery and molecular therapy. PATIENT CONCERNS: A 70-year-old man with postoperative history of prostate cancer experienced fast-growing malignant jejunal GIST with multiple peritoneal metastases within 1 year. DIAGNOSES: Enhanced computed tomography (CT) detected a neoplasm of small intestine with multiple peritoneal nodules and postoperative pathology confirmed GIST. INTERVENTIONS: Oral imatinib after surgery, at 400 mg per day, was used for 4 years. OUTCOMES: The patient remains well, and the peritoneal nodules located in front of the rectum disappeared gradually. LESSONS: Physicians should be aware of possibility of GIST in patients with prostate cancer and can perform abdominal examination in these patients. For postoperative patients with prostate cancer, an yearly or half-yearly abdominal and pelvic cavity examination can be performed. Suspicion and timely work-up is necessary in these postoperative prostate cancer patients, especially when they have abdominopelvic pain.

Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis.

Disseminated superficial actinic porokeratosis (DSAP) is an autosomal dominantly inherited epidermal keratinization disorder whose etiology remains unclear. We performed exome sequencing in one unaffected and two affected individuals from a DSAP family. The mevalonate kinase gene (MVK) emerged as the only candidate gene located in previously defined linkage regions after filtering against existing SNP databases, eight HapMap exomes and 1000 Genomes Project data and taking into consideration the functional implications of the mutations. Sanger sequencing in 57 individuals with familial DSAP and 25 individuals with sporadic DSAP identified MVK mutations in 33% and 16% of these individuals (cases), respectively. All 14 MVK mutations identified in our study were absent in 676 individuals without DSAP. Our functional studies in cultured primary keratinocytes suggest that MVK has a role in regulating calcium-induced keratinocyte differentiation and could protect keratinocytes from apoptosis induced by type A ultraviolet radiation. Our results should help advance the understanding of DSAP pathogenesis.

Association between alcohol, smoking and HLA-DQA1*0201 genotype in psoriasis.

Psoriasis is a chronic skin disease triggered by genetic, environment or other risk factors such as infection, drugs, stress, moisture, alcohol, and smoking. A major psoriasis susceptibility locus at 6p21.3 has been identified. Further studies found that HLA-DQA1*0201 allele was associated with psoriasis. However, there were few data exploring an association between the environmental factors and susceptibility genes. In this study, the samples of 189 patients with psoriasis and 333 healthy controls were collected with their consent and were carried on analysis through polymerase chain reaction sequence-specific primer (PCR-SSP) method. The proportion of male psoriasis patients engaging in the smoking and alcohol was much higher than that of the control group (P<0.005). The HLA-DQA1*0201 allele was present at significantly higher frequency in the patients with psoriasis (OR=4.25, P<1.0 x 10(-6)). Association was found between smoking, alcohol and HLA-DQA1*0201 in male patients with psoriasis (OR>6.91, P<1.0 x 10(-4)).

Identification of a locus for punctate palmoplantar keratodermas at chromosome 8q24.13-8q24.21.

Punctate palmoplantar keratodermas (PPK) is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules that are irregularly distributed on the palms and soles. The genetic basis for this disease is unknown. We performed a genome-wide search in two Chinese families with punctate PPK to map the chromosome location of the responsible gene. We identified a locus at chromosome 8q24.13-8q24.21 with a cumulative maximum two-point LOD score of 5.41 at markers D8S1793 and D8S1774 (at recombination fraction theta=0.00). Haplotype analysis indicated that the disease gene is located within 9.20 cM region between markers D8S1804 and D8S1720. It is the first locus identified for the punctate PPK. This study provides a map location for isolation of a disease gene-causing punctate PPK.

Association of HLA class I alleles with psoriasis vulgaris in southeastern Chinese Hans.

BACKGROUND: Predisposing genetic factors in psoriasis include associations with human leukocyte antigen (HLA). Accumulative evidence has shown that certain HLA at class I locus, especially HLA-Cw6, are associated closely with psoriasis. OBJECTIVE: To evaluate the association of HLA class I alleles with susceptibility to psoriasis in the southeastern Chinese Han population. METHODS: We performed genotype for HLA-A, -B and -C loci in 166 patients with psoriasis vulgaris by means of polymerase chain reaction with sequence-specific primers technique. The distribution of HLA allelic frequencies was further analyzed according to age of onset, i.e. under 35-y and beyond 35-y groups. These data were compared with the healthy controls of 204 unrelated Hans. RESULTS: The frequencies of HLA-A*26 (24.7% vs. 13.1%, OR=2.36, Pc<0.01), -B*13 (27.2% vs. 14.8%, OR=2.34, Pc<0.01), -B*27 (12.2% vs. 4.0%, OR=3.49, Pc<0.01) and -Cw*0602 (17.9% vs. 5.3%, OR=4.20, Pc<0.001) were significantly increased in psoriasis patients, whereas HLA-Cw*0304 frequency (4.9% vs. 13.4%, OR=0.32, Pc<0.01) was highly decreased, when compared to the controls. HLA-A*26-B*27-Cw*0602 was identified as a high-risk haplotype of HLA class I in developing psoriasis in the test. HLA-Cw*0602 was found to be strongly associated with the early-onset psoriasis (age of onset <35 y). CONCLUSION: This study demonstrated the positive associations of HLA class I markers with psoriasis vulgaris, of which HLA-Cw*0602 was the strongest susceptibility determinant for development of early-onset psoriasis, in the southeastern Chinese Han population.

Evidence for a major psoriasis susceptibility locus at 6p21(PSORS1) and a novel candidate region at 4q31 by genome-wide scan in Chinese hans.

Psoriasis is a heterogeneous disease with seven major psoriasis susceptibility loci reported so far on chromosomes 1p, 1q, 3q, 4q, 6p, 17q, and 19p, respectively. To investigate the psoriasis susceptibility loci in Chinese Hans, a genome-wide scan was performed with two-point and multipoint parametric and nonparametric linkage analyses in 61 multiplex families. These families were Chinese Hans residing in east and south-east China, comprising 189 affected and 166 unaffected individuals. We detected evidence for linkage at 6p21 (PSORS1) with nonparametric linkage scores > 3 in the range of 39.9-62.3 cM and a maximum multipoint nonparametric linkage score of 4.58 (p=0.000032). Parametric analysis revealed a maximum two-point heterogeneity lod score of 4.30 with 58% as the proportion of linked families (alpha) and a maximum multipoint heterogeneity lod score of 4.25 (alpha=53%) under the assumption of a dominant model. We could not confirm a previous reported locus (PSORS3) on distal chromosome 4q; however, a region of highly suggestive linkage was identified proximal to this proposed locus. Multipoint nonparametric analysis demonstrated nonparametric linkage scores > 3 throughout a region between 152.5 cM and 165.1 cM (from pter) with a maximum peak of 3.69 (p=0.00033) at 157.9 cM, which locates D4S413. A maximum multipoint heterogeneity lod score of 2.31 (alpha=46%) was reached at 163.1 cM. With two-point parametric linkage analysis, we observed the highest lod score of 2.43 and heterogeneity lod score of 3.94 (alpha=77%) at marker D4S1597. Our results showed that chromosomes 6p and 4q may contain genes involved in the susceptibility to psoriasis vulgaris in a Chinese Han population. Other regions with weaker evidence for linkage could also hide minor susceptibility genes.