Loryn N. Sellner

Distinction Between Intraductal Carcinoma of the Prostate (IDC-P), High-Grade Dysplasia (PIN), and Invasive Prostatic Adenocarcinoma, Using Molecular Markers of Cancer Progression

Prostate ducts and acini whose lumens are filled with malignant cells represent a well‐recognized histological pattern recently termed intraductal carcinoma of the prostate (IDC‐P). These tumors are often associated with rapid disease progression, and most recur after radical surgery. Controversy exists as to whether IDC‐P should be recognized as a separate entity, an extension of high‐grade dysplasia (PIN) or invasive carcinoma as described by the Gleason grading system. This study investigates the use of molecular markers in defining the position of IDC‐P in the evolutionary hierarchy of prostate cancer progression.

The use of optimal cutting temperature compound can inhibit amplification by polymerase chain reaction.

Optimal cutting temperature (OCT) is a widely used embedding medium for tissues for histopathologic analysis. This investigation examined the effects that OCT storage can have upon the ability to perform subsequent molecular biological analyses. Tumor material was dissected into small pieces and stored at −20°C both with and without OCT. DNA and RNA were then extracted from the tissue fragments and analyzed by the polymerase chain reaction (PCR), using primer sets designed to amplify a range of product sizes, and also by reverse transcriptase-PCR (RT-PCR). The storage of pathological specimens in OCT compound was found to affect significantly and irreversibly the ability to amplify DNA in the PCR, particularly as the size of the amplified fragment increased. This effect appeared to occur as a result of greater degradation of DNA extracted from tissue embedded in OCT compared to DNA extracted from tissue stored without OCT. RNA quality appeared unaffected, which may be because of the extraction protocol employed. Our results suggest that OCT-embedded frozen-tissue samples may be used for RNA isolation for subsequent RT-PCR and for the in vitro amplification of DNA targets of approximately < 300 base pairs only. We strongly advise against the routine storage of any tissue biopsy material in OCT if molecular analyses may be required.

The incidence of microsatellite instability and loss of heterozygosity in fibroadenoma of the breast

A majority of studies have shown an increase in the risk of breast cancer among women previously diagnosed with fibroadenoma (FA). At present there is conflicting evidence whether some of the chromosome abnormalities frequently found in breast carcinoma, such as loss of heterozygosity (LOH), are already present in FAs and other types of benign breast disease and, if present, whether such abnormalities are associated with the observed increase in risk. Microsatellite instability (MSI) is also recognised as a marker of genetic damage and is thought to occur when there has been damage to the cells mismatch repair (MMR) system. We have analysed 39 cases of FA obtained from paraffin-embedded tissue for the presence of MSI and LOH at 11 loci to determine if these types of genetic alterations occur in FA. The incidence of MSI and LOH found were 4 of 395 (1.0%) and 5 of 271 (1.8%) informative loci tested respectively. Approximately 8% of cases were positive for MSI and 10% were positive for LOH, with one specimen having multiple occurences of both MSI and LOH. We conclude that these forms of genetic alteration do occur in FAs but that the incidence is low.

Sarcomatoid Renal Cell Carcinoma of Papillary Origin A Case Report and Cytogenetic Evaluation

Sarcomatoid renal cell carcinoma (SRCC) is an aggressive tumor variant thought to arise predominantly from dedifferentiation of clear cell carcinoma. A few reports of SRCC associated with non-clear cell tumors led to the presumption that SRCC may arise from any renal cell carcinoma, although direct evidence of this is lacking. Cytogenetic studies on 3 previously documented SRCCs associated with papillary renal cancers showed either 3p deletions or absence of trisomy 7, 17 in the sarcomatoid tumors, suggesting origin from a coexistent clear cell tumor. The present case represents the first conclusive evidence of direct progression of non-clear cell carcinoma to SRCC with both tumor components containing multiple copies of chromosomes 7 and 17. Many genetic anomalies, including p53 mutations, frequently recognized in SRCC were not recognized in this case, highlighting the importance of cytogenetic evaluation of all SRCC. The patient is well and without evidence of tumor progression 1 year after surgery, and the sinister outlook of SRCC in association with clear cell carcinoma may not apply in SRCC of non-clear cell origin.

Variant Chromophobe Renal Cell Carcinoma. A morphology not recognized after routine fixation

Abstract Separation of renal cell tumors into different prognostic groups is an imperative function of the diagnostic pathologist. Recently, chromophobe renal carcinoma has been described as a tumor that is morphologically distinct from conventional “clear cell” carcinoma and that has a low metastatic potential. Identification is based on routine light microscopic features and is confirmed by special stains, immunohistochemistry, and electron microscopy. We present a variant of chromophobe renal carcinoma that did not show the typical cytomorphologic features on light microscopy after formaldehyde fixation. After fixation in Solufix (a commercial fixative), these features were recognized and the diagnosis was confirmed. The tumor also showed an unusual form of calcification and psammoma body formation not previously recognized in chromophobe tumors. Molecular biological assessment was inconclusive, but excluded a chromosome 3p deletion usually found in conventional renal carcinoma. The use of a different ...