The molecular pathology of hereditary breast cancer.

Hereditary breast cancer arising in carriers of mutations in the BRCA1 and BRCA2 genes differs from sporadic breast cancer and from non-BRCA1/2 familial breast carcinomas. Most BRCA1 carcinomas have the basal-like phenotype and are high-grade, highly proliferating, estrogen receptor-negative and HER2-negative breast carcinomas, characterized by the expression of basal markers such as basal keratins, P-cadherin and epidermal growth factor receptor. BRCA1 carcinomas frequently carry p53 mutations. The basal-like phenotype is only occasionally found in BRCA2 carcinomas, which tend to be estrogen and progesterone receptor positive. BRCA1 and BRCA2 loss of heterozygosity is found in almost all BRCA1 and BRCA2 carcinomas, respectively. Both genotypes have a low frequency of HER2 expression/amplification. In addition, comparative genomic hybridization and array expression studies have revealed differences in chromosomal gains and losses as well as expression patterns between genotypes. Several studies have shown that hereditary carcinomas that are not attributable to BRCA1/2 mutations are heterogeneous and have phenotypic similarities to BRCA2 tumors. A small group of cases are secondary to mutations in other breast cancer susceptibility genes, such as p53, PTEN or CDH1. As a result of the low frequency of breast carcinomas attributable to mutations in these genes, it is very difficult to establish a specific phenotype for each genotype, other than the association of lobular carcinomas with CDH1 germline mutations. The pathological and molecular features of hereditary breast cancer can drive specific treatments and influence the process of mutation screening.

Underexpression of peroxisome proliferator-activated receptor (PPAR)gamma in PAX8/PPARgamma-negative thyroid tumours.

The expression of peroxisome proliferator-activated receptor (PPAR)gamma in thyroid neoplasias and in normal thyroid (NT) tissues has not been fully investigated. The objectives of the present work were: to study and compare the relative expression of PPARgamma in normal, benign and malignant thyroid tissues and to correlate PPARgamma immunostaining with clinical/pathological features of patients with thyroid cancer. We analysed the expression of PPARgamma in several types of thyroid tissues by reverse transcription-polymerase chain reaction (RT-PCR), interphase fluorescent in situ hybridisation, real-time RT-PCR and immunohistochemistry. We have demonstrated that NT tissues express PPARgamma both at mRNA and at protein level. PAX8-PPARgamma fusion gene expression was found in 25% (six of 24) of follicular thyroid carcinomas (FTCs) and in 17% (six of 36) of follicular thyroid adenomas, but in none of the 10 normal tissues, 28 nodular hyperplasias, 38 papillary thyroid carcinomas (PTCs) and 11 poorly differentiated thyroid carcinomas (PDTCs). By real-time RT-PCR, we observed that tumours negative for the PAX8-PPARgamma rearrangement expressed lower levels of PPARgamma mRNA than the NT. Overexpression of PPARgamma transcripts was detected in 80% (four of five) of translocation-positive tumours. Diffuse nuclear staining was significantly (P<0.05) less prevalent in FTCs (53%; 18 of 34), PTCs (49%; 19 of 39) and PDTCs (0%; zero of 13) than in normal tissue (77%; 36 of 47). Peroxisome proliferator-activated receptorgamma-negative FTCs were more likely to be locally invasive, to persist after surgery, to metastasise and to have poorly differentiated areas. Papillary thyroid carcinomas with a predominantly follicular pattern were more often PPARgamma negative than classic PTCs (80% vs 28%; P=0.01). Our results demonstrated that PPARgamma is underexpressed in translocation-negative thyroid tumours of follicular origin and that a further reduction of PPARgamma expression is associated with dedifferentiation at later stages of tumour development and progression.

Diffuse uterine leiomyomatosis with ovarian and parametrial involvement.

BACKGROUND: Diffuse uterine leiomyomatosis is a rare, benign entity and approximately 30 cases have been described previously. CASE: A 42-year-old woman who complained of abdominal pain had a pelvic ultrasound scan showing a uterine mass. During the operation, the surgeon observed that both ovaries, the broad ligament, and the pelvis contained various nodules of striking size. On sectioning, uterus and ovaries contained multiple nodules of elastic consistency; microscopically, all consisted of benign smooth muscle tissue. CONCLUSION: Leiomyomatosis may exhibit concomitant parametrial, pelvic, and bilateral ovarian involvement.

[Multilocular renal cysts. Clinical and therapeutic considerations]. / Quiste multilocular renal. Reflexiones Clínico-Terapeúticas.

OBJECTIVE: According to current concepts, multilocular renal cysts are the most benign type of embryonary tumors by contrast to wilm's tumor. Our experience with multilocular renal cyst is presented herein. METHODS: 12 patients (4 boys, 6 adult females and two males) were diagnosed and treated for multilocular renal cyst. One of the adult male patients had an adenocarcinoma located on one of the cysts. Ten patients underwent nephrectomy and two patients were treated by conservative surgery. RESULTS: At 9 years' mean follow-up, no tumor recurrence has been observed. CONCLUSIONS: In the adult patient, all segmental, large and multiloculated cystic masses with a homogeneous content that do not compromise the rest of the parenchyma or adjacent organs except by compression, are suggestive of a multilocular cyst. Conservative surgery is the most reasonable therapeutic option if the foregoing is suspected. This condition has a very good long-term prognosis.