Clinical Relevance of Red Blood Cell Distribution Width (RDW) in Endometrial Cancer: A Retrospective Single-Center Experience from Korea.

BACKGROUND: Red blood cell distribution width (RDW) is a standard parameter of complete blood count and indicates the variability in red blood cell size. This study aimed to determine whether preoperative RDW can be used to predict the recurrence and prognosis of endometrial carcinoma. METHODS: The medical records of 431 patients diagnosed with endometrial carcinoma were retrospectively reviewed between May 2006 and June 2018. In addition to RDW, the clinicopathological factors, survival curves, and prognoses of the patients with endometrial carcinoma were compared between the high (n = 213) and low (n = 218) groups according to the median RDW value (12.8%). RESULTS: The patients with high RDW had significantly advanced-stage (p = 0.00) pelvic lymph node metastasis (p = 0.01) and recurrence (p = 0.01) compared to those in the low-RDW group. In univariate analysis with DFS as the endpoint, surgical stage, type II histology, grade, RDW, and lymph node metastasis were independently associated with survival. Patients with high RDW values had significantly shorter disease-free survival and overall survival than those with low RDW values (log-rank p = 0.03, log-rank p = 0.04, respectively). CONCLUSION: Our results demonstrate that RDW is a simple and convenient indicator of endometrial carcinoma recurrence. Prospective studies are needed to validate the findings of the current study.

Expression Profiles of ID and E2A in Ovarian Cancer and Suppression of Ovarian Cancer by the E2A Isoform E47.

The E2A and inhibitor of DNA binding (ID) proteins are transcription factors involved in cell cycle regulation and cellular differentiation. Imbalance of ID/E2A activity is associated with oncogenesis in various tumors, but their expression patterns and prognostic values are still unknown. We evaluated ID and E2A expression in ovarian cancer cells, and assessed the possibility of reprogramming ovarian cellular homeostasis by restoring the ID/E2A axis. We analyzed copy number alterations, mutations, methylations, and mRNA expressions of ID 1-4 and E2A using The Cancer Genome Atlas data of 570 ovarian serous cystadenocarcinoma patients. Incidentally, 97.2% cases exhibited gain of ID 1-4 or loss of E2A. Predominantly, ID 1-4 were hypomethylated, while E2A was hypermethylated. Immunohistochemical analysis revealed that ID-3 and ID-4 expressions were high while E2A expression was low in cancerous ovarian tissues. Correlation analysis of ID and E2A levels with survival outcomes of ovarian cancer patients indicated that patients with high ID-3 levels had poor overall survival. We also determined the effect of E2A induction on ovarian cancer cell growth in vitro and in vivo using SKOV-3/Luc cells transduced with tamoxifen-inducible E47, a splice variant of E2A. Interestingly, E47 induced SKOV-3 cell death in vitro and inhibited tumor growth in SKOV-3 implanted mice. Therefore, restoring ID/E2A balance is a promising approach for treating ovarian cancer.

Nationwide Comparison of Surgical and Oncologic Outcomes in Endometrial Cancer Patients Undergoing Robotic, Laparoscopic, and Open Surgery: A Population-Based Cohort Study.

PURPOSE: Population-based comparisons between minimally invasive surgery (MIS) (robotic surgery [RS] and laparoscopic surgery [LS]) and open surgery (OS) for managing endometrial cancer are lacking. This study aimed to compare surgical and oncologic outcomes between endometrial cancer patients who underwent surgical staging via MIS or OS. MATERIALS AND METHODS: A population-based retrospective cohort study was performed using claims data from the Korean National Health Insurance database from January 2012 to December 2016. All patients who underwent hysterectomy under diagnosis of endometrial cancer were identified. Patients were classified into RS, LS, and OS groups. Operative and oncologic outcomes were compared among the three groups after adjustments for age group, risk group (adjuvant therapy status), modified Charlson comorbidity index, income level, insurance type, and index year using propensity scores obtained via the inverse probability of treatment weighted method. RESULTS: After adjustment, 5,065 patients (RS, n=315; LS, n=3,248; OS, n=1,503) were analyzed. Patient demographics were comparable. Hospital stay, postoperative complications, and cost were more favorable in the RS and LS groups than in the OS group (all p < 0.001). Five-year overall survival was significantly longer in the RS and LS groups than in the OS group (94.8%, 91.9%, and 86.9%, respectively; p < 0.001). Moreover, the survival benefit of RS was shown in the subgroup analysis of low-risk endometrial cancer patients. CONCLUSION: Our study provides further evidence for the RS being a safe surgical alternative to the LS and OS, especially in low-risk endometrial cancer patients, offering surgical and oncologic outcomes equivalent to other surgical approaches.

Pretreatment neutrophil-to-lymphocyte ratio and its dynamic change during neoadjuvant chemotherapy as poor prognostic factors in advanced ovarian cancer.

OBJECTIVE: The purpose of this study was to determine the prognostic implications of the pretreatment neutrophil-to-lymphocyte ratio (NLR) and its dynamic change during chemotherapy in patients with advanced epithelial ovarian cancer undergoing neoadjuvant chemotherapy. METHODS: We performed a retrospective analysis of 203 patients who underwent neoadjuvant chemotherapy prior to interval debulking surgery for advanced-stage ovarian cancer at Yonsei Cancer Hospital between 2007 and 2015. Pretreatment NLR was evaluated before starting neoadjuvant chemotherapy. Change in NLR was defined as the post-neoadjuvant NLR value divided by the initial value. The correlation of NLR and its dynamic change with chemotherapy response score, response rate, and recurrence was analyzed. RESULTS: The NLR ranged from 0.64 to 22.8. In univariate analyses, a higher pretreatment NLR (>3.81) was associated with poor overall survival (OS), but not progression-free survival (PFS). Through multivariate analysis, high pretreatment NLR was shown to be an independent parameter affecting OS, but not necessarily PFS. Changes in NLR during chemotherapy were better predictors of PFS than baseline NLR. Patients with increased NLR during chemotherapy showed significantly poor PFS, and this change was an independent predictor of PFS. CONCLUSION: Pretreatment NLR and its dynamic change during chemotherapy may be important prognostic factors in patients who undergo neoadjuvant chemotherapy.

A screen for inducers of bHLH activity identifies pitavastatin as a regulator of p21, Rb phosphorylation and E2F target gene expression in pancreatic cancer.

The average survival for patients with Pancreatic Ductal Adenocarcinoma (PDA) is merely 6 months, underscoring the need for new therapeutic approaches. During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo. To translate these findings for clinical utility, we developed a high throughput screening platform to identify small molecule inducers of Class I/II bHLH activity. A screen of 4,375 known drugs identified 70 bHLH activators. Prominent among the hits were members of the statin class of HMG-CoA reductase inhibitors, cholesterol lowering drugs that are also being evaluated in cancer. Studies with pitavastatin in primary patient derived tumor cells and established PDA lines, revealed dose dependent growth inhibition. At the molecular level, pitavastatin induced expression of the cyclin dependent kinase (CDK) inhibitor p21 in a cholesterol independent manner, blocked repressive phosphorylation of the Retinoblastoma tumor suppressor protein at CDK targeted sites, and reduced expression of E2F target genes required for progression through the G1/S boundary. Together, the data provide new insight into mechanisms by which statins constrain proliferation in cancer and establish the effectiveness of a novel screening platform to identify small molecules of clinical relevance in pancreatic cancer.

Role of systematic lymphadenectomy as part of primary debulking surgery for optimally cytoreduced advanced ovarian cancer: Reappraisal in the era of radical surgery.

The prognostic significance of pelvic and para-aortic lymphadenectomy during primary debulking surgery for advanced-stage ovarian cancer remains unclear. This study aimed to evaluate the survival impact of lymph node dissection (LND) in patients treated with optimal cytoreduction for advanced ovarian cancer. Data from 158 consecutive patients with stage IIIC-IV disease who underwent optimal cytoreduction (<1 cm) were obtained via retrospective chart review. Patients were classified into two groups: (1) lymph node sampling (LNS), node count <20; and (2) LND, node count ≥20. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Among the included patients, 96 and 62 patients underwent LND and LNS as primary debulking surgery, respectively. There were no differences in the extent of debulking surgical procedures, including extensive upper abdominal surgery, between the groups. Patients who underwent LND had a marginally significantly improved PFS (P = 0.059) and significantly improved OS (P < 0.001) compared with those who underwent LNS. In a subgroup with negative lymphadenopathy on preoperative computed tomography scans, revealed LND correlated with a better PFS and OS (P = 0.042, 0.001, respectively). Follow-ups of subsequent recurrences observed a significantly lower nodal recurrence rate among patients who underwent LND. A multivariate analysis identified LND as an independent prognostic factor for PFS (hazard ratio [HR], 0.629; 95% confidence interval [CI], 0.400-0.989) and OS (HR, 0.250; 95% CI, 0.137-0.456). In conclusion, systematic LND might have therapeutic value and improve prognosis for patients with optimally cytoreduced advanced ovarian cancer.

The basic helix-loop-helix transcription factor E47 reprograms human pancreatic cancer cells to a quiescent acinar state with reduced tumorigenic potential.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDA) initiates from quiescent acinar cells that attain a Kras mutation, lose signaling from basic helix-loop-helix (bHLH) transcription factors, undergo acinar-ductal metaplasia, and rapidly acquire increased growth potential. We queried whether PDA cells can be reprogrammed to revert to their original quiescent acinar cell state by shifting key transcription programs. METHODS: Human PDA cell lines were engineered to express an inducible form of the bHLH protein E47. Gene expression, growth, and functional studies were investigated using microarray, quantitative polymerase chain reaction, immunoblots, immunohistochemistry, small interfering RNA, chromatin immunoprecipitation analyses, and cell transplantation into mice. RESULTS: In human PDA cells, E47 activity triggers stable G0/G1 arrest, which requires the cyclin-dependent kinase inhibitor p21 and the stress response protein TP53INP1. Concurrently, E47 induces high level expression of acinar digestive enzymes and feed forward activation of the acinar maturation network regulated by the bHLH factor MIST1. Moreover, induction of E47 in human PDA cells in vitro is sufficient to inhibit tumorigenesis. CONCLUSIONS: Human PDA cells retain a high degree of plasticity, which can be exploited to induce a quiescent acinar cell state with reduced tumorigenic potential. Moreover, bHLH activity is a critical node coordinately regulating human PDA cell growth versus cell fate.

Learning curve and surgical outcome for single-port access total laparoscopic hysterectomy in 100 consecutive cases.

AIMS: To define the learning curve for single-port access (SPA) total laparoscopic hysterectomy (TLH) and evaluate the surgical outcomes. METHODS: Patient demographics and segmental operating times of all 100 patients who underwent SPA-TLH by a single surgeon were analyzed. Patients were arranged in order based on surgery date. RESULTS: 100 patients underwent SPA-TLH. There was no conversion to conventional laparoscopy or laparotomy. The median time until the removal of a specimen (T(R)) was 45 min and the median time for closure of the vaginal cuff (T(C)) was 18 min. The median total operating time from skin opening to closure (T(O)) was 80 min. T(R), T(C), and T(O) decreased significantly over the study period. The T(C) decreased significantly from the first 20 cases to the next 20 (p = 0.028) and the T(O) from the second 20 cases to the next 20 (p = 0.029). CONCLUSIONS: Proficiency for SPA-TLH was achieved after 40 cases. Operating time and postoperative hemoglobin drop decreased with experience, without increasing complication.

Prognostic significance of human epididymis protein 4 in epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to evaluate the prognostic significance of serum human epididymis protein 4 (HE4) level in patients with epithelial ovarian cancer. STUDY DESIGN: A total of 78 women diagnosed with a pelvic mass and operated on in our institute comprised our cohort. Forty-five of these were diagnosed with epithelial ovarian cancer and treated with debulking surgery, followed by taxane and platinum-based chemotherapy as clinically indicated. Preoperatively obtained serum samples were analyzed for levels of HE4 and CA125. RESULTS: The elevated serum HE4 level was related to advanced stage and serous type of cancer. The median duration of the follow-up was 35.1 months. In advanced stage, the median progression-free survival (PFS) of patients with elevated serum HE4 levels was 20.1 months (95% CI, 15.7-24.6 months), whereas that of patients with normal serum HE4 level was 24.2 months (95% CI, 13.9-34.6 months) (p=0.029). Independent predictors for PFS in patients with advanced stage EOC included serum HE4 level (hazard ratio 2.24; 95% CI, 1.14 to 6.84; p=0.048). CONCLUSIONS: Our results demonstrated that an elevated serum HE4 level was related to the advanced stage of epithelial ovarian cancer. An elevated serum level of HE4 is a poor prognostic factor for PFS in patients with epithelial ovarian cancer who were treated with debulking surgery and adjuvant taxane and platinum-based chemotherapy. The serum HE4 level is a promising indicator for the progression of cancer as well as a biomarker for the detection of epithelial ovarian cancer.

Differential effect of intraperitoneal albendazole and paclitaxel on ascites formation and expression of vascular endothelial growth factor in ovarian cancer cell-bearing athymic nude mice.

OBJECTIVES: The purposes of our study were to evaluate the effect of intraperitoneal albendazole on tumor growth, ascites formation, and vascular endothelial growth factor (VEGF) mRNA expression, and to assess the synergistic effect of paclitaxel in OVCAR-3-bearing nude mice. METHODS: In all, 4 groups of mice were injected intraperitoneally with weekly albendazole (450 mg/kg per week), paclitaxel (30 mg/kg per week), albendazole plus paclitaxel, or normal saline for 4 weeks. RESULTS: Ascitic fluid accumulation (2.47, 2.65, 2.88, and 5.90 mL, respectively) and in ascitic VEGF levels were significantly reduced in the 3 treatment groups compared to the control group (170.83, 229.16, 267, and 1625 pg/mL, respectively). However, complete tumor suppression was more prominent in the paclitaxel group, and VEGF mRNA expression was more strongly inhibited in the albendazole group (P < .05). No synergistic effect of albendazole and paclitaxel was observed. CONCLUSION: We demonstrated a differential effect of albendazole and paclitaxel in a xenograft model of ovarian carcinoma; albendazole suppressed ascites formation by inhibiting VEGF secretion, and paclitaxel exerted its effects by direct cytotoxicity.

The feasibility of carboplatin-based intraperitoneal chemotherapy in ovarian cancer.

OBJECTIVE: To reduce toxicities in cisplatin-based intraperitoneal (IP) chemotherapy, we substituted carboplatin for cisplatin. The purpose of this study was to provide preliminary toxicity data of carboplatin-based IP chemotherapy and to evaluate the feasibility of this chemotherapy regimen in patients with ovarian cancer after primary debulking surgery. STUDY DESIGN: The toxicity data of 19 primary ovarian cancer patients (IP group) who underwent carboplatin-based IP and intravenous (IV) combination chemotherapy (IP carboplatin AUC 5 on day 1, IV paclitaxel 175mg/m² on day 2, and IP paclitaxel 60mg/m² on day 8) after primary debulking surgery were retrospectively analyzed and compared to 34 patients (IV group) who were treated with standard platinum-based IV chemotherapy during the same period. RESULTS: The toxicity data in a total of 118 cycles were analyzed. Grade 3 or 4 leukopenia, neutropenia, and pain were more common in the IP group than the IV group. There were seven catheter-related complications. Fourteen patients (73.7%) were able to complete six cycles or more of IP chemotherapy. Survival results in the IP group were compared with those from the IV group; a prolonged progression-free survival was observed (26.6 vs. 20.7 months; p=0.038). Compared to the previous results with cisplatin-based IP chemotherapy, there was no significant difference in hematologic events. However, gastrointestinal, neurologic, and metabolic events in this study were definitely lower compared to those of cisplatin-based IP chemotherapy. CONCLUSIONS: Carboplatin-based IP and IV combination chemotherapy is feasible in patients with ovarian carcinoma after primary debulking surgery.

Clinical significance of microsatellite instability in sporadic epithelial ovarian tumors.

PURPOSE: We evaluated the expression of microsatellite instability (MSI) in sporadic ovarian tumors using 5 standard and 9 new MSI markers to determine the clinical significance of MSI in sporadic epithelial ovarian tumors. MATERIALS AND METHODS: MSI was examined in 21 borderline and 25 malignant ovarian tumors. Polymerase chain reaction (PCR) was performed using the 5 markers recommended by the National Cancer Institute (NCI) for colon cancer and 9 additional markers. MSI was determined using fractional analysis by mixing the PCR products and size markers. RESULTS: Using the 5 conventional MSI markers, MSI was found in 4 of 46 (8.6%) ovarian tumors, including 2 of 21 (9.5%) borderline ovarian tumors and 2 of 25 (8%) malignant ovarian tumors. Using the 9 additional MSI markers, MSI was observed in 7 of 46 (15.2%) ovarian tumors, including 3 of 21 (14.3%) borderline ovarian tumors and 4 of 25 (16%) malignant ovarian tumors. There was no statistically significant difference between MSI and clinicopathological factors, including histology and stage, although there was a trend toward an increased incidence of MSI in the serous type. CONCLUSION: MSI was infrequent in ovarian tumors, including both borderline and malignant tumors. MSI was found to be uncommon in sporadic ovarian tumors, even by using additional MSI markers. The clinical significance of MSI is not strong in patients with sporadic ovarian tumors.

A case of placenta increta presenting as delayed postabortal intraperitoneal bleeding in the first trimester.

Placenta increta is an uncommon and life-threatening complication of pregnancy characterized by complete or partial absence of the decidua basalis. Placenta increta usually presents with vaginal bleeding during difficult placental removal in the third-trimester. Although placenta increta may complicate first and early second-trimester pregnancy loss, the diagnosis can be very difficult during early pregnancy and thus the lesion is difficult to identify. We encountered with a woman who was diagnosed with placenta increta after receiving emergency hysterectomy due to intraperitoneal bleeding 2 months after an uncomplicated dilatation and curettage in the first trimester. Therefore, we report this case with a brief review of the literature.

Structural and functional analyses of mutations of the human phenylalanine hydroxylase gene.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism that results from a deficiency of phenylalanine hydroxylase (PAH). We demonstrated PAH mutational spectrum from patients with PKU, including 10 novel and 3 tetrahydrobiopterin (BH(4))-responsive mutations. In this study, 11 PAH missense mutations, including 6 novel mutations (P69S, G103S, L293M, G332V, S391I, A447P) found in our previous study, 2 mutations common in east Asian patients with PKU (R243Q, R413P), and 3 tetrahydrobiopterin (BH(4))-responsive mutations (R53H, R241C, R408Q) have been functionally and structurally analyzed. METHODS: A transient protein overexpression system and an in vitro BH(4)-responsiveness study were used. The effects of PAH missense mutations on the PAH protein structure were also analyzed. To determine the conservation of 12 mutated residues, PAH was aligned using BLAST against full genomic sequences of 221 different species. Model structures of PAH protein and the composite tetramer were constructed using the software program, SHEBA. RESULTS: No PAH activity was detected for some mutants. However, the residual activities associated with other mutants ranged over a wide spectrum. The missense mutations responsive to BH(4) were not highly conserved throughout the 43 species in the multiple sequence alignment that encode PAH. The composite model structure of PAH revealed that dimer stability was reduced in the BH(4)-responsive mutants, whereas tetramer stability remained normal. CONCLUSION: This expression study analyzed PAH mutations and model structures of mutant PAH proteins are proposed. Correlation between the proposed mutant PAH structures and functions are suggested.

Quantitative analysis of SMN1 gene and estimation of SMN1 deletion carrier frequency in Korean population based on real-time PCR.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder, caused by homozygous absence of the survival motor neuron gene (SMN1) in approximately 94% of patients. Since most carriers have only one SMN1 gene copy, several SMN1 quantitative analyses have been used for the SMA carrier detection. We developed a reliable quantitative real-time PCR with SYBR Green I dye and studied 13 patients with SMA and their 24 parents, as well as 326 healthy normal individuals. The copy number of the SMN1 gene was determined by the comparative threshold cycle (Ct) method and albumin was used as a reference gene. The homozygous SMN1 deletion ratio of patients was 0.00 and the hemizygous SMN1 deletion ratio of parents ranged from 0.39 to 0.59. The deltadelta Ct ratios of 7 persons among 326 normal individuals were within the carrier range, 0.41-0.57. According to these data, we estimated the carrier and disease prevalence of SMA at 1/47 and 1/8,496 in Korean population, respectively. These data indicated that there would be no much difference in disease prevalence of SMA compared with western countries. Since the prevalence of SMA is higher than other autosomal recessive disorders, the carrier detection method using real-time PCR could be a useful tool for genetic counseling.

The molecular basis of phenylketonuria in Koreans.

Phenylketonuria (PKU) is an inborn error of metabolism that results from a deficiency of phenylalanine hydroxylase (PAH). We characterized the PAH mutations of 79 independent Korean patients with PKU or hyperphenylalaninemia. PAH nucleotide sequence analysis revealed 39 different mutations, including ten novel mutations. The novel mutations consisted of nine missense mutations (P69S, G103S, N207D, T278S, P281A, L293M, G332V, S391I, and A447P) and a novel splice site variant (IVS10-3C>G). R243Q, IVS4-1G>A, and E6-96A>G were the most prevalent mutations, as they accounted for 32% of the total mutant alleles in this study. Although some common characteristics of allele frequency and distribution were identified among oriental populations, several distinctive characteristics were revealed in Korean patients. Although the R413P allele is the most prevalent form (30.5%) in Japanese, we detected it in only five chromosomes from 158 independent chromosomes (3.2%). The A259T allele, which has not yet been found in oriental populations, was frequently found in this study. We also observed that tetrahydrobiopterin (BH4) responsiveness was associated with specific genotypes (R53H, R241C, and R408Q), suggesting there are some correlations between phenotype and genotype.

Patterns of treatment failure following radiotherapy with combination chemotherapy for patients with high-risk stage IIB cervical carcinoma.

BACKGROUND: To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy. METHODS: A retrospective analysis of 349 patients with stage IIB cervical carcinoma with high-risk factors (lesion size >/= 4 cm, lymph node metastasis, high-risk cell type) treated by radiotherapy and cisplatin-based chemotherapy was performed. Sites of treatment failure were categorized as pelvic, pelvic plus distant metastases, and distant metastases alone. Pelvic failure included local and pelvic nodal failures. RESULTS: Of the 349 patients, treatment failure occurred in 79 patients (22.6%). Forty-six (13.2%) had persistent disease and 33 (9.5%) had recurrent disease. Among these 79 patients, overall pelvic failure was observed in 67%, of whom 72% had local failure; 19%, pelvic nodal failure; and 9%, local with pelvic nodal failure. Incidences of distant metastases alone and pelvic with distant metastases were 24% and 9%. In the 26 patients with distant metastases either alone or combined with pelvic failure, the most frequent metastatic region was the paraaortic lymph node (50%). The distant metastasis rate was 6.5% (19/289) in the pelvic tumor control group and 11.6% (7/60) in the pelvic failure group. Pelvic failure was the most frequent failure in the group with tumor size of 4 cm or more, whereas, for the positive-lymph-node group, distant metastasis was most frequent and metastases to paraaortic lymph nodes were common. The incidences of pelvic failure alone and distant metastases were similar in the high-risk cell-type group, and the distant metastasis regions were mostly paraaortic lymph nodes. CONCLUSION: Although systemic chemotherapy was administered concurrently with radiotherapy, the incidence of pelvic failure was highest, followed by paraaortic lymph node metastases, in patients with stage IIB cervical carcinoma with high-risk factors, following radiotherapy with combination chemotherapy. To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy.

Rapid detection of duplication/deletion of the PMP22 gene in patients with Charcot-Marie-Tooth disease Type 1A and hereditary neuropathy with liability to pressure palsy by real-time quantitative PCR using SYBR Green I dye.

Mutations and altered gene dosage of the peripheral myelin protein (PMP22) gene in chromosome 17p11.2-12 are the main causes for hereditary neuropathies, accounting for approximately 70% of all cases. Patients with duplication of the PMP22 develop Charcot-Marie-Tooth disease type 1A (CMT1A) and deletion of one PMP22 allele leads to hereditary neuropathy with liability to pressure palsy (HNPP). Twenty patients with CMT1A, 17 patients with HNPP, and 18 normal family members and 28 normal controls were studied by real-time quantitative PCR using SYBR Green I on the ABI 7700 Sequence Detection System. The copy number of the PMP22 gene was determined by the comparative threshold cycle method and the albumin was used as a reference gene. The PMP22 duplication ratio ranged from 1.45 to 2.06 and the PMP22 deletion ratio ranged from 0.42 to 0.64. The PMP22 ratio in normal controls, including normal family members, ranged from 0.85 to 1.26. No overlap was found between patients with CMT1A or patients with HNPP and normal controls. This method is fast, highly sensitive, specific, and reproducible in detecting PMP22 duplication and deletion in CMT1A and HNPP patients, respectively.