Mismatch repair system in colorectal cancer. Frequency, cancer phenotype, and follow-up.

INTRODUCTION AND AIMS: A frequent task in the study of colorectal carcinomas (CRC) is to identify tumors harboring deficient DNA mismatch repair systems (dMMR), which are associated with microsatellite instability. Given that there is scant information on those tumors in Mexican patients, our aim was to describe their frequency, clinical and pathologic characteristics, and results, which are necessary for future trials. MATERIALS AND METHODS: A consecutive series of CRC patients, treated and followed at a tertiary care center was performed. The clinical and pathologic variables and the risk of hereditary or familial cancer syndrome were retrieved. The original slides and hMLH1, hPMS2, hMSH2, hMSH6 immunohistochemistry were evaluated. Tumors with an absence of at least one protein were considered dMMR. Differences were contrasted, utilizing non-parametric tests. RESULTS: One hundred and forty-four patients were included, with a median age of 65 years. A total of 134/93% patients presented with sporadic CRC, 8/5.6% had a family history of CRC, and 2/1.4% met the diagnostic criteria for hereditary non-polyposis colon cancer, according to the Amsterdam and Bethesda criteria. dMMR tumors were found in 39 patients, distributed among the three groups. They were locally advanced (p<0.001), right-sided, had the mucinous phenotype, and harbored a Crohn's-like lymphoid reaction (all three features, p<0.04). Adjuvant or palliative chemotherapy was administered to 57 (39.6%), concomitant chemoradiotherapy to 24 (16.7%), but 63 (43.8%) patients received no additional treatment to surgery. Five-year follow-up was completed in 131 of the patients and the outcomes alive-with-disease or died-of-disease were more frequently observed in the proficient (pMMR) lesions. CONCLUSIONS: In the present pre-FOLFOX case series, outcomes were better in dMMR CRC than in proficient lesions.

Case-control analysis of fundic gland polyps and proton-pump inhibitors. A pathologist's perspective. / Análisis de casos y controles de pólipos de glándulas fúndicas e inhibidores de bomba de protones. La perspectiva de un patólogo.

INTRODUCTION AND AIM: Adequately preserved slides and tissue blocks in pathology archives, when re-reviewed and associated with patient charts, are important tools to further assess prevalence changes and associations of certain pathologies. Our aim was to identify whether proton-pump inhibitor (PPI) use, dose, and duration of use were associated with gastric polyps and their phenotypes in a case-control study. METHODS: The slides from patients with a morphologic diagnosis of either hyperplastic polyps or fundic gland polyps were retrieved from the 1980, 1990, 2000, 2010, and 2016 surgical pathology files at a tertiary care hospital in Mexico City and re-evaluated. Cases were paired by age and sex with patients that underwent endoscopy and gastric mucosa biopsy in the same year, with no evidence of polyps. RESULTS: A total of 133 (3.8%) patients with gastric polyps were identified from 3,499 gastric biopsies taken in the abovementioned years and compared with 133 paired controls. Dyspepsia was more prevalent in the controls (p=0.002) and abdominal pain was more prevalent in the patients with gastric polyps (p=0.001). PPI use (OR 7.7, 95% confidence interval, 4.4-13.3) and taking more than one PPI medication (OR 4.9, 95% confidence interval, 1.09-22.3) were significantly associated with the presence of gastric polyps. The fundic gland phenotype in the oxyntic mucosa was more frequently associated with PPI use (p<0.042), with a continuous increase in its prevalence starting in the year 2000 (p=0.017 for trend). CONCLUSION: PPI administration for at least one year was associated with gastric fundic gland polyps.

Atypical manifestations of hepatitis A virus infection. / Manifestaciones atípicas de la infección por el virus de la hepatitis A.

Acute hepatitis due to the hepatitis A virus usually has a short, benign and self-limited course, without causing chronic hepatitis. However, some cases have an atypical presentation, such as relapsing hepatitis, prolonged or persistent cholestasis, fulminant hepatic failure, or liver failure associated with autoimmune hepatitis. The typical clinical course of acute hepatitis A virus infection is spontaneous remission in 90% of the cases, but atypical cases have a prevalence that varies from less than 1 to 20%, depending on the manifestation (overall prevalence ∼7%). There is little information on the atypical clinical courses of hepatitis A virus infection and the lack of recognizing those presentations in clinical practice often results in carrying out numerous studies and treatments that not only are unnecessary, but can also be harmful. The aim of the present article was to describe 3 clinical cases of atypical hepatitis A infection and provide a literature review of such cases.

Achalasia--An Autoimmune Inflammatory Disease: A Cross-Sectional Study.

Idiopathic achalasia is a disease of unknown etiology. The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism. Thirty-two patients diagnosed by high-resolution manometry with achalasia were included. Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control). Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed. Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence. Herpes simplex virus-1 (HSV-1) infection was determined by in situ hybridization, RT-PCR, and immunohistochemistry. Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%). Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregs versus controls (P < 0.001). Circulating Th22/Th17/Th2/Th1 percentage showed a significant increase versus healthy donors (P < 0.01). Type III achalasia patients exhibited the highest inflammatory response versus types I and II. Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100% versus 0% in controls. Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection.

KCNH1 potassium channels are expressed in cervical cytologies from pregnant patients and are regulated by progesterone.

Potassium voltage-gated channel, subfamily H (eag-related), member 1 (KCNH1) potassium channels are potential tumour markers and cancer therapeutic targets and are up-regulated by oestrogens and human papilloma virus (HPV) oncogenes. However, the role of KCNH1 in normal tissues is poorly understood, and its expression in pregnancy is unknown. We wondered whether KCNH1 channels are expressed in cervical cells from pregnant patients and whether progesterone (P4) regulates KCNH1. The association with HPV was also investigated. KCNH1 protein expression was studied by immunocytochemistry in liquid-based cervical cytologies; 93 samples were obtained from pregnant patients at different trimesters, and 15 samples were obtained from non-pregnant women (controls). The presence of HPV was studied by PCR with direct sequencing and nested multiplex PCR. HeLa cervical cancer cells were transfected with human progesterone receptor-B (PR-B) and treated with P4. KCNH1 mRNA expression in these cultures was studied by real-time PCR. KCNH1 protein was detected in 100% of the pregnancy samples and in 26% of the controls. We found 18 pregnant patients infected with HPV and detected 14 types of HPV. There was no association between the percentage of cells expressing KCNH1 and either the presence or type of HPV. P4 induced KCNH1 mRNA and protein expression in cells transfected with human PR-B. No regulation of KCNH1 by P4 was observed in non-transfected cells. We show for the first time the expression of an ion channel during human pregnancy at different trimesters and KCNH1 regulation by P4 in human cells. These data raise a new research field for KCNH1 channels in human tissues.

Differential expression of functionality markers in mid-secretory endometrium of infertile women under treatment with ovulation-inducing agents.

OBJECTIVES: To analyze the expression of protein markers related to cell proliferation and death, as well as oestrogen and progesterone receptors in the endometrium of infertile women with hypothalamic-pituitary dysfunction treated with clomiphene citrate (CC) or recombinant follicle-stimulating hormone (rFSH), and compare them with ovulatory women. STUDY DESIGN: The study included 12 control ovulatory women and 29 anovulatory women, 19 of whom underwent ovulation induction with CC (n = 12) or rFSH (n = 5). Endometrial biopsies were obtained by Pipelle during the mid-secretory phase. Samples were stained with haematoxylin and eosin. Immunohistochemistry of proteins related to cell proliferation and cell death, as well as steroid receptors, was undertaken, and apoptosis was determined using TUNEL analysis. RESULTS: Immunohistochemical analysis of Ki67 expression showed significantly higher expression in the glandular epithelium of ovulatory women compared with the other groups. Glandular oestrogen receptor α expression was significantly lower in rFSH-treated women compared with ovulatory women. The number of apoptotic cells, Bax expression and progesterone receptor expression were similar in all groups. In contrast, Bcl-2 expression was significantly lower in the glandular epithelium of rFSH-treated women. CONCLUSIONS: In infertile women with hypothalamic-pituitary dysfunction, treatment with ovulation-inducing agents modifies the expression of proteins involved in cell proliferation and death, as well as the expression of steroid hormone receptors in the endometrium. These differences may help to explain, at the molecular level, the functionality of the endometrium during the implantation window, and may help to optimize pregnancy rates obtained with these treatments.

47 year-old man with HIV infection and hemiplegia.

CNS aspergillosis is often missed in the setting of advanced HIV infection, especially in the absence of presumed risk factors such as neutropenia or prior steroid treatment. We describe the postmortem evaluation of the brain of a patient with AIDS that developed progressive neurologic deterioration. Sequence brain MRIs, CSF analysis, and multiple presumed treatments failed to reveal the possible causes or improve his ongoing condition. His brain autopsy showed numerous abscesses with septated hyphae consistent with CNS angioinvasive aspergillosis.

[Pancreatic-duodenectomy for invasive colon cancer in a patient with Lynch syndrome. Case report.]. / Pancreatoduodenectomía por cáncer de colon invasor en un paciente con síndrome de Lynch; informe de un caso.

Despite the screening efforts in the general population and particularly in families with hereditary colon cancer, locally advanced colon cancer remains a common clinical problem. In block resection is considered mainstay therapy in these patients. The aim of this report is to present a case of right-sided colon cancer with a medullar phenotype invading the duodenum treated through in block resection. A case of a 54-year-old male with a family history of colon and pancreatic cancer with lower gastrointestinal tract bleeding is presented. Colonoscopy and computed tomography scan showed a tumor in the colonic hepatic flexure invading the duodenum. The patient underwent an in block resection of the right colon, duodenum, pancreas and antrum. The histopathological study showed a T4N0M0 adenocarcinoma invading the duodenum, pancreas and antrum with negative margins. His postoperative evolution was complicated with a pancreatic fistula, which resolved with conservative measures. In conclusion, in block resection is the treatment of choice for locally advanced colon cancer with invasion to duodenum and pancreas and should be performed in high-volume centers familiar with this type of procedures. Key words: pancreaticoduodenectomy, colon cancer, Lynch syndrome, pancreas, surgery, Mexico.

[Pyoderma gangrenosum peristomal in ulcerative colitis; first report of a case in Mexico]. / Pioderma gangrenoso periestomal en colitis ulcerativa; primer reporte de un caso en México.

Pyoderma gangrenosum is one of the most severe extraintestinal manifestations in patients with ulcerative colitis (UC) and Crohn s disease. This lesion is frequently located on the lower extremities and the torso. Peristomal pyoderma gangrenosum (PPG) is extremely rare. We report the first published patient with PPG and UC in Mexico. PPG occurred six weeks after restorative proctocolectomy. Diagnosis was performed by clinical presentation and biopsy. Ulcer resolution was achieved with oral steroids and local wound care. Patient did not show any recurrence at one year follow-up. We suggest suspecting this illness in all patients with UC who had a restorative proctocolectomy and present difficult management peristomal ulcers.

Clinical and pathological factors associated with the development of hepatocellular carcinoma in patients with hepatitis virus-related cirrhosis: a long-term follow-up study.

AIMS: Hepatocellular carcinoma (HCC) represents >90% of primary liver neoplasms and develops mainly in patients with liver cirrhosis. Risk factor identification for the development of HCC in patients with cirrhosis possesses great clinical relevance due to its high incidence and poor prognosis when detected at advanced stages. The aim of this study was to identify HCC development-associated risk factors in a cohort of patients with hepatitis virus-related chronic liver disease and cirrhosis. MATERIALS AND METHODS: Patients with a diagnosis of hepatitis virus-related cirrhosis between January 1980 and January 2000 were included. Patients were followed with an abdominal ultrasound and the determination of alpha-fetoprotein levels, a physical examination, and routine biochemical tests every 3-6 months. The end point of the study was defined as the development of HCC. Liver histology was evaluated according to the French METAVIR Cooperative Study Group (METAVIR) score. RESULTS: Two hundred and eighty-two patients met the inclusion criteria; most of these (86%) had a serologic diagnosis of hepatitis C virus, and only 14% had hepatitis B virus at the time of the diagnosis of cirrhosis, whereas 56 and 37% were classified as Child A and B, respectively, and only 7% as Child C. Histological activity was mild in 59% of patients, and moderate and severe in 41%. The mean annual incidence was 1.87%, and 22 and 35% of patients developed HCC at 10 and 15 years of follow-up, respectively. The diagnosis of HCC was made by histopathology in 37% and by tumoural lesion-associated alpha-fetoprotein elevation confirmed by imaging studies in 63%. In multivariate analysis, we found three variables associated with HCC: moderate to severe histological activity; a platelet count <105x10(3)/mm(3), and alpha-fetoprotein >5 ng/ml. The patients were divided into two groups according to regression coefficient: low and high risk; patients assigned to the low-risk group showed 5-, 10- and 15-year HCC incidences of 3.4, 6.4 and 6.4%, respectively, in contrast to patients from the high-risk group, who showed incidences of 17.8, 33.5 and 56.8%, respectively. CONCLUSIONS: We found three HCC-associated variables: histological activity, platelet count and alpha-fetoprotein levels. Patients considered as high risk for developing HCC must be considered candidates for closer follow-up.

Cytochrome P450 expression in rat gastric epithelium with intestinal metaplasia induced by high dietary NaCl levels.

Drug metabolizing enzymes like cytochrome P450 (CYP) play an important role in determining the susceptibility of organs or tissue to the toxic effects of drugs or other xenobiotics. There is some evidence indicating that individual isoforms of CYPs are over-expressed in different types of malignant tumors including that of oesophagus, pancreas, breast, lung, colon and stomach. Nevertheless, it is not clear if this change in expression is previous or after the appearance of malignancy. This is important in order to clarify the possible role of xenobiotics in the development of gastric cancer. On the other hand, it has been reported that a high salt ingestion leads to histological changes in rat stomach mucosa including enhanced cell proliferation, lipid peroxidation and intestinal metaplasia. The aim of this study is to explore the expression and activity of CYP families involved in the metabolism of carcinogens in normal rat stomach mucosa and intestinal metaplasia induced by high NaCl ingestion. Male Wistar rats were exposed to diets containing different NaCl concentrations (0.6% control group, 6%, 12%, 18% and 24%) for 12 weeks and histological changes as well as CYP modulation were monitored in gastric mucosa. Chronic gastritis, regenerative hyperplasia and focal metaplasia were noted in animals receiving the 12%, 18% and 24% NaCl diets. In the same groups, induction of CYP1A1 and CYP3A2 was produced, mainly in areas of metaplasia. The expression of xenobiotic metabolizing enzymes in the gastric mucosa might contribute to chemical activation in the stomach, metabolizing both exogenous and endogenous compounds implicated in the development of gastric cancer.

Carcinoid tumors of the duodenum and ampulla of vater: a clinicomorphologic, immunohistochemical, and cell kinetic comparison.

Carcinoid tumors of the ampulla of Vater (ACs) differ from duodenal carcinoid tumors (DCs). A search for AC and DC was made between 1980 and 2000. The clinicopathologic features and follow-up were assessed. Immunohistochemistry for panneuroendocrine markers, hormone products, proliferating cell nuclear antigen (PCNA), Ki- 67, p21(cip1), and p27(kip1) were performed. A blind proliferative index counting 500 cells was made. Differences were contrasted using the Fisher exact and 2-sided Student t test. Five ACs and 8 DCs were identified in 9 women and 4 men with median ages of 59 and 64 years and mean tumor diameters of 1.6 and 1.85 cm, respectively. All patients with AC presented jaundice, and most patients with DC were asymptomatic (P = .047). Metastases were present in 4 ACs and 1 DC (P =.03). Tumor cells expressed synaptophysin and chromogranin in 60% of ACs and in 100% and 87% of DCs. Gastrin was expressed in 75% of DCs and 20% of ACs (P < .05). The mean value for PCNA index was 4.0% in ACs and 3.2% in DCs, and mean values for Ki-67 were 12.2% and 10.2%, respectively (P = NS). Expression of p21(cip1) and p27(kip1) was observed in 40% of ACs and 37.5% and 12.5% of DCs. Three of 5 patients with AC died of the disease within an average of 11 months, and none of the patients with DC had died at 103 months of follow-up. The more aggressive behavior of ACs is not associated with higher proliferative indices or with different expression of cell cycle inhibitors.

p53 Mutations in nasal natural killer/T-cell lymphoma from Mexico: association with large cell morphology and advanced disease.

Nasal NK/T-cell lymphoma is a unique form of lymphoma highly associated with Epstein-Barr virus, and with a characteristic geographic distribution. Recently, we showed that p53 is overexpressed in a high percentage of nasal NK/T-cell lymphomas. The aim of this study was to analyze the status of the p53 gene, and correlate it with the expression of p53 protein and its downstream target, the cyclin-dependent kinase inhibitor p21, in a series of 25 cases of well-characterized nasal NK/T-cell lymphoma from Mexico. The highly conserved exons 5 to 8 of the p53 gene were amplified by polymerase chain reaction and screened for mutations by denaturing high-pressure liquid chromatography. Abnormal polymerase chain reaction products detected by denaturing high-pressure liquid chromatography and additional selected cases were sequenced. In addition, the incidence of loss of heterozygosity at the p53 locus was analyzed in 12 cases. Of the 25 patients, 17 were male and 8 female (M:F ratio, 2.1:1), with a median age of 43 years (range, 21 to 93 years). Morphologically, most of the cases were composed of a mixture of medium-sized cells and large transformed cells (21 cases), and four cases were composed exclusively of large transformed cells. Three different groups determined by p53 gene status and expression of p53 protein were identified: group 1 was p53 +/p53 mutated (five cases, all with p53 missense mutations). Morphologically, three of the five cases were composed of large cells. All five cases revealed overexpression of p53 in the majority of the tumor cells with a mean of 86%. Unexpectedly, three of these cases also showed overexpression of p21. Four of the five patients presented with clinical stage IVB and died with disease. Group 2 was p53+/p53 wild-type (10 cases). Histologically, nine cases were of the mixed type, and one of the large cell type. The percentage of p53 overexpressing cells was lower than in the previous group with a mean of 23%. p21 was positive in 7 of the 10 cases. Six patients in this group presented with clinical stages I to II and four patients with advanced disease (stage III and IV). Five patients are alive 12 to 120 months later (mean, 24 months), three with no evidence of disease. Group 3 was p53-/p53 wild-type (10 cases). All cases showed mixed cell morphology. p21 was positive in 5 of 10 cases. Four patients presented with clinical stage I to II and six patients with advanced disease. Four patients are alive with no evidence of disease 9 to 60 months later (mean, 10 months). Overall, p53 mutations were present in 24% (5 of 21) of the evaluable cases, all of them overexpressing p53 in the majority of tumor cells. Cases with p53 mutations were associated with large cell morphology (P = 0.0162) and presented more often with advanced stage disease. Loss of heterozygosity at chromosome 17p was found only in 2 of the 12 (17%) cases investigated, both cases showed p53 mutations of the remaining allele. P21 overexpression (60% of cases) is frequent in nasal NK/T-cell lymphoma and seems to be independent of p53 gene status. The overexpression of p53 and p21, independent of p53 mutations, although as yet not clear, might be the result of Epstein-Barr virus infection, and warrants further investigation.

Accuracy of sentinel lymph node in papillary thyroid carcinoma.

BACKGROUND: The sentinel lymph node has been used in several tumors. The aim of this study was to analyze the accuracy of the sentinel node in papillary thyroid carcinoma. METHODS: A series of 22 patients with papillary thyroid carcinoma were included. Approximately 0.5 cc of isosulfan blue dye was injected at operation to trace the sentinel node. Lymph node dissection of the ipsilateral central compartment and extensive sampling of the jugular compartment were performed in addition to sentinel node resection. Surgical specimens were stained with hematoxylin-eosin, and negative sentinel nodes were subsequently stained with immunohistochemistry for cytokeratin-7. RESULTS: Mean age was 37 +/- 14 years. Twenty patients were women, and 2 were men. Mean tumor size was 2.5 +/- 1 cm. A sentinel lymph node was found in 20 patients. With use of hematoxylin-eosin, metastases were identified in 12/20 sentinel nodes (60%). Eleven patients with positive sentinel nodes presented additional lymph node metastases: 9 in the central compartment, 1 in the jugular compartment, and 1 in both compartments. Two patients with negative sentinel nodes had lymph node metastases elsewhere. When sentinel nodes were processed by immunohistochemistry, accuracy increased to 100%. CONCLUSIONS: Sentinel node is highly accurate for diagnosing metastases in papillary thyroid carcinoma.

Sporadic type composite pheochromocytoma with neuroblastoma: clinicomorphologic, DNA content and ret gene analysis.

Composite pheochromocytomas (CP) account for only 3% of all pheochromocytomas. We analyzed the clinical, immunohistochemical, ultrastructural, DNA content, and 634 ret mutation features in a 56-year-old Mexican woman with CP localized in the right adrenal gland and associated to a blood pressure of 140/90 mmHg. Clinical symptoms were absent after surgery. The tumor showed pheochromocytoma and neuroblastoma components. This dual phenotype was supported by light microscopy and corroborated by immunohistochemistry and ultrastructural findings. Flow cytometric analysis showed that both components were diploid. A genetic mutational analysis of the ret oncogene in exon 11 showed no 634 mutation. This case demonstrates the indolent behavior of neuroblastoma associated to a sporadic-type CP in an adult patient.

Progesterone receptor isoforms expression pattern in human astrocytomas.

Progesterone receptors (PR) have been detected in human astrocytomas; however, the expression pattern of PR isoforms in these brain tumors is unknown. Progesterone receptor isoforms expression was studied in 13 biopsies of astrocytomas (6 grade III, and 7 grade IV) from adult Mexican patients by using reverse transcription-polymerase chain reaction and immunohistochemistry. Progesterone receptor expression was observed at mRNA and at protein levels in 66% and 83% of astrocytomas grade III, respectively, whereas 100% of astrocytomas grade IV expressed PR. Almost all PR mRNA content in astrocytomas grades III and IV corresponded to PR-B. The number of immunoreactive cells expressing PR-B was higher than that expressing PR-A in 73% of the cases. Estrogen receptor-alpha protein was only observed in 33% of astrocytomas grade III, whereas no astrocytomas grade IV expressed it. These data suggest that PR-B is the predominant isoform expressed in human astrocytomas grades III and IV, and that estrogen receptor-alpha is not expressed in astrocytomas grade IV.

Histologic diagnosis of primary hyperparathyroidism: a concordance analysis between three pathologists.

Primary hyperparathyroidism (HPT) is caused by a parathyroid adenoma, hyperplasia or carcinoma. Difficulties for the histologic diagnosis of abnormal parathyroid tissue are widely recognized. The aim of the study was to evaluate the reproducibility of the morphologic criteria through a concordance study among three pathologists. Representative slides of 40 patients with biochemically primary HPT stained with hematoxylin and eosin were blindly reviewed by three pathologists. Each pathologist established the diagnosis of adenoma or hyperplasia and assessed the presence of fat cells, a rim of normal tissue, a fibrous capsule, the number of cellular types, the lobular pattern, and the characteristics of the blood vessel's wall. A concordance analysis was then performed. Mean age of the group was 55 +/- 14 yr, 7 were males and 33 females. The concordance analysis among the three pathologists for the differential diagnosis between adenoma and hyperplasia, showed a Kappa index of 0.5. Kappa index for the presence of fat cells was 0.56, for the presence of a rim of normal tissue 0.47, and for the number of cellular types 0.29. The concordance for the differential diagnosis between parathyroid adenoma and hyperplasia in this study was low.

Progesterone receptor isoforms expression pattern in human chordomas.

Steroid hormone receptors are involved in the regulation of tumor growth. Two progesterone receptor (PR) isoforms have been identified in humans: a larger form (PR-B) and the N-terminally truncated one (PR-A). PR isoforms can exert opposite functions and are differentially regulated by estrogens. PR have been detected in several brain tumors including chordomas, however, it is unknown which PR isoform is expressed in brain tumors. The aim of this study was to determine by reverse transcription-polymerase chain reaction (RT-PCR) and by immunohistochemistry the expression pattern of PR isoforms in chordomas as well as its correlation with the expression of estrogen receptor a (ER-alpha). All studied chordomas expressed both PR and ER-alpha. PR-B was the predominant isoform in chordomas both at the mRNA and at the protein level. These data suggest that PR-B should be the predominant PR isoform expressed in human chordomas.